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Sample records for 5-hydroxytryptamine uptake sites

  1. In vivo labeling of 5-hydroxytryptamine uptake sites in mouse brain with ( sup 3 H)-6-nitroquipazine

    SciTech Connect

    Hashimoto, K.; Goromaru, T. )

    1990-10-01

    6-Nitroquipazine (DU 24565; 6-nitro 2-piperazinylquinoline) is a very potent 5-hydroxytryptamine (5-HT; serotonin) uptake inhibitor. It has been demonstrated very recently that (3H)-6-nitroquipazine is a suitable radioligand for studying 5-HT uptake sites. The present study evaluates (3H)6-nitroquipazine as a radioligand for in vivo labeling of 5-HT uptake sites in mouse brain. Very high uptake of radioactivity in the brain after i.v. administration of (3H)-6-nitroquipazine was shown. Regional distribution of the radioactivity in mouse brain 3 hr after injection of (3H)-6-nitroquipazine was in the order (highest to lowest) hypothalamus greater than midbrain greater than striatum greater than hippocampus greater than cerebral cortex greater than medulla oblongata greater than cerebellum. The regional distribution of in vivo (3H)-6-nitroquipazine binding in mouse brain was highly correlated with that in rat brain obtained from previous in vitro binding studies. Coadministration of carrier 6-nitroquipazine (5 mg/kg) significantly decreased the radioactivity in the hypothalamus, whereas that in the cerebellum and cerebral cortex was increased. Because the cerebellum has very low density of (3H)-6-nitroquipazine binding sites, the radioactivity in the cerebellum could, therefore, reflect the amount on nonspecific binding and free ligand. Kinetic studies showed highest in vivo specific binding 1 hr after injection of (3H)-6-nitroquipazine and slow clearance of specific binding. Specific binding in the hypothalamus was inhibited in a stereoselective manner by the stereoisomers of norzimelidine. Furthermore, specific binding in the hypothalamus was reduced by several 5-HT uptake inhibitors, in a dose-dependent manner.

  2. Uptake of 5-hydroxytryptamine in different parts of the brain of the rabbit after intraventricular injection.

    PubMed Central

    Dow, R C; Laszlo, I

    1976-01-01

    1 The uptake of 5-hydroxytryptamine (5-HT) was investigated in different areas of the rabbit brain (anterior hypothalamus, the raphe, the region of the substantia nigra, several cortical areas and the medulla oblongata) after intraventricular injection in pargyline pretreated animals by the formaldehyde-induced histochemical fluorescence method. 2 The distribution of fluorescence showed that the uptake of 5-HT, after circulation in the cerebrospinal fluid, caused a general increase in intensity of green yellow to yellow background fluorescence. There was an increased fluorescence in the nerve terminals, but no uptake occurred either in the cell bodies of neurones or in the glial cells. Images Figure 1 Figure 2 PMID:1260225

  3. Selective irreversible blockade of 5-hydroxytryptamine1A and 5-hydroxytryptamine1C receptor binding sites in the rat brain by 8-MeO-2'-chloro-PAT: a quantitative autoradiographic study.

    PubMed

    Radja, F; Daval, G; Emerit, M B; Gallissot, M C; Hamon, M; Vergé, D

    1989-01-01

    The possible irreversible blockade of 5-hydroxytryptamine1 receptor subtypes 5-hydroxytryptamine1A, 5-hydroxytryptamine1B/5-hydroxytryptamine1D and 5-hydroxytryptamine1C by the chloramine 8-methoxy-2-(N-2'-chloropropyl,N-propyl)aminotetralin (8-MeO-2'-chloro-PAT) was investigated in rat brain sections by quantitative autoradiography using [3H]8-hydroxy-2-(di-n-propylamino)tetralin [( 3H]8-OH-DPAT), [3H]5-hydroxytryptamine, [125I]BH-8-MeO-N-PAT and [125I]cyanopindolol as radio-ligands. A marked reduction (-50% to -75%) of [3H]8-OH-DPAT and [125I]BH-8-MeO-N-PAT specific binding to 5-hydroxytryptamine1A sites in the hippocampus (CA1 area) and the dorsal raphe nucleus, and of [3H]5-hydroxytryptamine specific binding to 5-hydroxytryptamine1C sites in the choroid plexus was found in sections exposed to 1 microM 8-MeO-2'-chloro-PAT and then washed extensively. In contrast the specific binding of [3H]5-hydroxytryptamine to 5-hydroxytryptamine1B/5-hydroxytryptamine1D sites and of [125I]cyanopindolol to 5-hydroxytryptamine1B sites in the substantia nigra and dorsal subiculum remained unaltered by this treatment. Similarly [125I]cyanopindolol binding to beta-adrenergic receptors was not affected by 8-MeO-2'-chloro-PAT. Prior occupancy of 5-hydroxytryptamine1A sites by 10 microM 5-hydroxytryptamine or 8-OH-DPAT, and of 5-hydroxytryptamine1C sites by 10 microM 5-hydroxytryptamine prevented any subsequent blockade by 8-MeO-2'-chloro-PAT. These data indicate that 8-MeO-2'-chloro-PAT should be a useful alkylating agent for achieving selective irreversible blockade of central 5-hydroxytryptamine1A and 5-hydroxytryptamine1C receptors in vivo in the rat. PMID:2531850

  4. 5-Hydroxytryptamine

    PubMed Central

    Curzon, G.; Fernando, J.C.R.; Marsden, C.A.

    1978-01-01

    1 Control rats given L-tryptophan (100 mg/kg) showed a smaller increase of brain 5-hydroxytryptamine (5-HT) than its metabolite 5-hydroxyindoleacetic acid (5-HIAA). However, when brain 5-HT concentrations were depleted by 40-50% after treatment with the synthesis inhibitor p-chlorophenylalanine (PCPA) (150 mg/kg) L-tryptophan caused a considerable increase in 5-HT but no change in 5-HIAA. Similar results were obtained following depletion of brain 5-HT by pretreatment with p-chloroamphetamine (10 mg/kg). 2 Electrical stimulation of the median raphe nucleus of control rats significantly increased 5-HIAA in the hypothalamus, hippocampus and striatum. However, stimulation of PCPA (200 mg/kg) pretreated animals did not significantly increase 5-H1AA either 24 or 72 h after administration of the drug. 3 Pretreatment of rats with PCPA (200 mg/kg) increased striatal synaptosomal uptake of [3H]-5HT by 30% and reduced 5-HT concentration in the rest of the brain by 62%. 4 PCPA (150 mg/kg) markedly reduced the acute behavioural response (-76%) to p-chloroamphetamine (10 mg/kg) although brain 5-HT was only moderately reduced (-36%). L-Tryptophan (100 mg/kg) given 15 min before p-chloroamphetamine restored both brain 5-HT and the behavioural effects of p-chloroamphetamine in PCPA pretreated rats and enhanced the behavioural response to p-chloroamphetamine in control rats. 5 The results suggest that newly synthesized 5-HT is less rapidly metabolized in rats with low brain 5-HT. The possible reasons for this and the relevance of the results to the use of L-tryptophan in the treatment of depressive illness are discussed. PMID:80243

  5. Activation of human 5-hydroxytryptamine type 3 receptors via an allosteric transmembrane site.

    PubMed

    Lansdell, Stuart J; Sathyaprakash, Chaitra; Doward, Anne; Millar, Neil S

    2015-01-01

    In common with other members of the Cys-loop family of pentameric ligand-gated ion channels, 5-hydroxytryptamine type 3 receptors (5-HT3Rs) are activated by the binding of a neurotransmitter to an extracellular orthosteric site, located at the interface of two adjacent receptor subunits. In addition, a variety of compounds have been identified that modulate agonist-evoked responses of 5-HT3Rs, and other Cys-loop receptors, by binding to distinct allosteric sites. In this study, we examined the pharmacological effects of a group of monoterpene compounds on recombinant 5-HT3Rs expressed in Xenopus oocytes. Two phenolic monoterpenes (carvacrol and thymol) display allosteric agonist activity on human homomeric 5-HT3ARs (64 ± 7% and 80 ± 4% of the maximum response evoked by the endogenous orthosteric agonist 5-HT, respectively). In addition, at lower concentrations, where agonist effects are less apparent, carvacrol and thymol act as potentiators of responses evoked by submaximal concentrations of 5-HT. By contrast, carvacrol and thymol have no agonist or potentiating activity on the closely related mouse 5-HT3ARs. Using subunit chimeras containing regions of the human and mouse 5-HT3A subunits, and by use of site-directed mutagenesis, we have identified transmembrane amino acids that either abolish the agonist activity of carvacrol and thymol on human 5-HT3ARs or are able to confer this property on mouse 5-HT3ARs. By contrast, these mutations have no significant effect on orthosteric activation of 5-HT3ARs by 5-HT. We conclude that 5-HT3ARs can be activated by the binding of ligands to an allosteric transmembrane site, a conclusion that is supported by computer docking studies. PMID:25338672

  6. Relative activities on and uptake by human blood platelets of 5-hydroxytryptamine and several analogues

    PubMed Central

    Born, G. V. R.; Juengjaroen, Kanchana; Michal, F.

    1972-01-01

    1. The specificity of platelet receptor sites for 5-HT uptake and for the rapid morphological change and aggregation was investigated with 5-hydroxy-tryptamine (5-HT) and seventeen analogues as well as with some antagonists of 5-HT. 2. The analogues, with the exception of 5-hydroxy-N'N'-dibutyltryptamine, caused the rapid morphological change in platelets. In concentrations below those needed to produce the agonistic action (viz. 0.05-2.0 μM), these analogues themselves inhibited competitively the shape change caused by 5-HT. 3. The velocity of change in shape caused by 5-HT was reduced in low Na media. 4. Ten analogues produced platelet aggregation; three of these, viz. 5-methoxy-α-methyltryptamine, 5-hydroxy-α-methyltryptamine and 5-hydroxy-N'N'-diisopropyltryptamine), were approximately equipotent with 5-HT. Six analogues did not induce platelet aggregation. 5. All the analogues which prevented the initial change in shape of platelets caused by 5-HT also inhibited its aggregating effect, apparently competitively with low Ki values (0.02-1.6 μM). 6. As with the inhibition of shape change, the inhibition of aggregation shows relatively low structural specificity of the receptor site. 7. Methysergide was a potent inhibitor of shape change and aggregation (Ki∼0.03 μM); imipramine was much less inhibitory (Ki∼5-10 μM). 8. Only one analogue (5-hydroxy-α-methyltryptamine) was taken up like 5-HT by platelets. All the other analogues inhibited the uptake of 5-HT by platelets (Ki=0.2-2.7 μM). 9. Methysergide was a weak inhibitor of 5-HT uptake (Ki∼125 μM) whereas imipramine was very effective (Ki∼0.3 μM). 10. Our results show that the initial change in shape of platelets is required for and precedes aggregation. The structural specificity of the platelet receptor concerned with shape change and aggregation caused by 5-HT appears low whereas the uptake mechanism is a highly specific one. The uptake probably proceeds through more than one step, the

  7. Relative activities on and uptake by human blood platelets of 5-hydroxytryptamine and several analogues.

    PubMed

    Born, G V; Juengjaroen, K; Michal, F

    1972-01-01

    1. The specificity of platelet receptor sites for 5-HT uptake and for the rapid morphological change and aggregation was investigated with 5-hydroxy-tryptamine (5-HT) and seventeen analogues as well as with some antagonists of 5-HT.2. The analogues, with the exception of 5-hydroxy-N'N'-dibutyltryptamine, caused the rapid morphological change in platelets. In concentrations below those needed to produce the agonistic action (viz. 0.05-2.0 muM), these analogues themselves inhibited competitively the shape change caused by 5-HT.3. The velocity of change in shape caused by 5-HT was reduced in low Na media.4. Ten analogues produced platelet aggregation; three of these, viz. 5-methoxy-alpha-methyltryptamine, 5-hydroxy-alpha-methyltryptamine and 5-hydroxy-N'N'-diisopropyltryptamine), were approximately equipotent with 5-HT. Six analogues did not induce platelet aggregation.5. All the analogues which prevented the initial change in shape of platelets caused by 5-HT also inhibited its aggregating effect, apparently competitively with low K(i) values (0.02-1.6 muM).6. As with the inhibition of shape change, the inhibition of aggregation shows relatively low structural specificity of the receptor site.7. Methysergide was a potent inhibitor of shape change and aggregation (K(i) approximately 0.03 muM); imipramine was much less inhibitory (K(i) approximately 5-10 muM).8. Only one analogue (5-hydroxy-alpha-methyltryptamine) was taken up like 5-HT by platelets. All the other analogues inhibited the uptake of 5-HT by platelets (K(i)=0.2-2.7 muM).9. Methysergide was a weak inhibitor of 5-HT uptake (K(i) approximately 125 muM) whereas imipramine was very effective (K(i) approximately 0.3 muM).10. Our results show that the initial change in shape of platelets is required for and precedes aggregation. The structural specificity of the platelet receptor concerned with shape change and aggregation caused by 5-HT appears low whereas the uptake mechanism is a highly specific one. The

  8. The effect of selective 5-hydroxytryptamine uptake inhibitors on 5-methoxy-N,N-dimethyltryptamine-induced ejaculation in the rat.

    PubMed Central

    Rényi, L.

    1986-01-01

    The ejaculatory response and the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-1 i.p.) were studied following acute and repeated treatment of rats with the selective uptake inhibitors of 5-HT, fluoxetine, zimeldine, alaproclate, and citalopram. The oral doses used were based on the respective ED50 values for uptake inhibition. Acute doses of fluoxetine and zimeldine significantly reduced the ejaculatory response when given 48 h before 5-MeODMT. This blockade was prevented by treatment of the rats with the postsynaptic 5-HT receptor antagonist methergoline. An acute dose of fluoxetine given 7 and 14 days before 5-MeODMT significantly enhanced the ejaculatory response. On day 24, the response returned to the control level. Repeated treatment every second day (5 times over 9 days and 10 times over 19 days) with fluoxetine caused a longer blockade of the ejaculatory response and the sensitization of the response came later than after an acute dose. Parallel with the ejaculatory response three other components of the 5-HT behavioural syndrome also decreased significantly. Acute doses of alaproclate and citalopram significantly blocked the ejaculatory response at 1 h, but they failed to affect the response at any other time point after either acute or repeated treatment. Neither did these drugs attentuate the 5-HT syndrome. It is concluded that acute and repeated treatment of rats with different selective 5-HT uptake inhibitors does not produce a common alteration in 5-HT2-receptor functions. PMID:2939912

  9. The effect of selective 5-hydroxytryptamine uptake inhibitors on 5-methoxy-N,N-dimethyltryptamine-induced ejaculation in the rat.

    PubMed

    Rényi, L

    1986-04-01

    The ejaculatory response and the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-1 i.p.) were studied following acute and repeated treatment of rats with the selective uptake inhibitors of 5-HT, fluoxetine, zimeldine, alaproclate, and citalopram. The oral doses used were based on the respective ED50 values for uptake inhibition. Acute doses of fluoxetine and zimeldine significantly reduced the ejaculatory response when given 48 h before 5-MeODMT. This blockade was prevented by treatment of the rats with the postsynaptic 5-HT receptor antagonist methergoline. An acute dose of fluoxetine given 7 and 14 days before 5-MeODMT significantly enhanced the ejaculatory response. On day 24, the response returned to the control level. Repeated treatment every second day (5 times over 9 days and 10 times over 19 days) with fluoxetine caused a longer blockade of the ejaculatory response and the sensitization of the response came later than after an acute dose. Parallel with the ejaculatory response three other components of the 5-HT behavioural syndrome also decreased significantly. Acute doses of alaproclate and citalopram significantly blocked the ejaculatory response at 1 h, but they failed to affect the response at any other time point after either acute or repeated treatment. Neither did these drugs attentuate the 5-HT syndrome. It is concluded that acute and repeated treatment of rats with different selective 5-HT uptake inhibitors does not produce a common alteration in 5-HT2-receptor functions. PMID:2939912

  10. Interaction of tryptamine and ergoline compounds with threonine 196 in the ligand binding site of the 5-hydroxytryptamine6 receptor.

    PubMed

    Boess, F G; Monsma, F J; Meyer, V; Zwingelstein, C; Sleight, A J

    1997-09-01

    We examined the ligand-binding site of the 5-hydroxytryptamine6 (5-HT6) receptor using site-directed mutagenesis. Interactions with residues in two characteristic positions of trans-membrane region V are important for ligand binding in several bioamine receptors. In the 5-HT6 receptor, one of these residues is a threonine (Thr196), whereas in most other mammalian 5-HT receptors, the corresponding residue is alanine. After transient expression in human embryonic kidney 293 cells, we determined the effects of the mutation T196A on [3H]d-lysergic acid diethylamide (LSD) binding and adenylyl cyclase stimulation. This mutation produced a receptor with a 10-fold reduced affinity for [3H]LSD and a 6-fold reduced affinity for 5-HT. The potency of both LSD and 5-HT for stimulation of adenylyl cyclase was also reduced by 18- and 7-fold, respectively. The affinity of other N1-unsubstituted ergolines (e.g., ergotamine, lisuride) was reduced 10-30 fold, whereas the affinity of N1-methylated ergolines (e.g., metergoline, methysergide, mesulergine) and other ligands, such as methiothepine, clozapine, ritanserin, amitriptyline, and mainserin, changed very little or increased. This indicates that in wild-type 5-HT6 receptor, Thr196 interacts with the N1 of N1-unsubstituted ergolines and tryptamines, probably forming a hydrogen bond. Based on molecular modeling, a serine residue in transmembrane region IV of the 5-HT2A receptor has previously been proposed to interact with the N1-position of 5-HT. When the corresponding residue of the 5-HT6 receptor (Ala154) was converted to serine, no change in the affinity of twelve 5-HT6 receptor ligands or in the potency of 5-HT and LSD could be detected, suggesting that this position does not contribute to the ligand binding site of the 5-HT6 receptor. PMID:9284367

  11. Platelet-induced neurogenic coronary contractions due to accumulation of the false neurotransmitter, 5-hydroxytryptamine.

    PubMed Central

    Cohen, R A

    1985-01-01

    The purpose of this study was to determine if 5-hydroxytryptamine released from aggregating platelets could be accumulated and released by canine coronary adrenergic nerves, and if the false neurotransmitter resulted in an abnormal response of the smooth muscle to nerve stimulation. Isometric tension was measured in rings of epicardial coronary suspended in organ chambers filled with physiological salt solution. The response to electrical stimulation or exogenously added norepinephrine was elicited after contraction with prostaglandin F2 alpha. Electrical stimulation and exogenous norepinephrine caused beta-adrenergic relaxation of control rings. However, after rings were exposed for 2 h to aggregating platelets or 5-hydroxytryptamine, electrical stimulation caused frequency-dependent contractions. These contractions were prevented by the serotonergic antagonists, cyproheptadine or ketanserin, or by the neuronal uptake inhibitor, cocaine. The relaxation caused by exogenously added norepinephrine was unchanged after exposure to platelets or 5-hydroxytryptamine, indicating that smooth muscle alpha- and beta-adrenergic responsiveness was unchanged. The electrically stimulated overflow of radiolabeled norepinephrine from superfused strips of coronary artery was not altered by prior exposure to 5-hydroxytryptamine, indicating that the effect of exposure on the response to electrical stimulation is primarily at smooth muscle serotonergic receptors. Canine coronary arteries accumulated and metabolized radiolabeled 5-hydroxytryptamine in vitro. The accumulation of 5-hydroxytryptamine was inhibited by cocaine or by adrenergic denervation with 6-hydroxydopamine but unaffected by removal of endothelium, indicating that the adrenergic nerves were the primary site of accumulation. Electrical stimulation of superfused strips of coronary artery preincubated with radiolabeled 5-hydroxytryptamine caused the release of the intact indoleamine; this was blocked by the neurotoxin

  12. Neuropharmacology of 5-hydroxytryptamine

    PubMed Central

    Richard Green, A

    2006-01-01

    This review outlines the history of our knowledge of the neuropharmacology of 5-hydroxytryptamine (5-HT; serotonin), focusing primarily on the work of U.K. scientists. The existence of a vasoconstrictive substance in the blood has been known for over 135 years. The substance was named serotonin and finally identified as 5-HT in 1949. The presence of 5-HT in the brain was reported by Gaddum in 1954 and it was Gaddum who also demonstrated that the action of 5-HT (in the gut) was antagonised by the potent hallucinogen lysergic acid diethylamide. This provoked the notion that 5-HT played a pivotal role in the control of mood and subsequent investigations have generally confirmed this hypothesis. Over the last 50 years a good understanding has been gained of the mechanisms involved in control of the storage, synthesis and degradation of 5-HT in the brain. Knowledge has also been gained on control of the functional activity of this monoamine, often by the use of behavioural models. A considerable literature also now exists on the mechanisms by which many of the drugs used to treat psychiatric illness alter the functional activity of 5-HT, particularly the drugs used to treat depression. Over the last 20 years the number of identified 5-HT receptor subtypes has increased from 2 to 14, or possibly more. A major challenge now is to utilise this knowledge to develop receptor-specific drugs and use the information gained to better treat central nervous system disorders. PMID:16402098

  13. Mapping the binding site pocket of the serotonin 5-Hydroxytryptamine2A receptor. Ser3.36(159) provides a second interaction site for the protonated amine of serotonin but not of lysergic acid diethylamide or bufotenin.

    PubMed

    Almaula, N; Ebersole, B J; Zhang, D; Weinstein, H; Sealfon, S C

    1996-06-21

    Like other amine neurotransmitters that activate G-protein-coupled receptors, 5-hydroxytryptamine (5-HT) binds to the 5-HT2A receptor through the interaction of its cationic primary amino group with the conserved Asp3.32(155) in transmembrane helix 3. Computational experiments with a 5-HT2A receptor model suggest that the same functional group of 5-hydroxytryptamine also forms a hydrogen bond with the side chain of Ser3.36(159), which is adjacent in space to Asp3.32(155). However, other 5-HT2A receptor ligands like lysergic acid diethylamide (LSD), in which the amine nitrogen is embedded in a heterocycle, or N,N-dimethyl 5-HT, in which the side chain is a tertiary amine, are found in the computational simulations to interact with the aspartate but not with the serine, due mainly to steric hindrance. The predicted difference in the interaction of various ligands in the same receptor binding pocket was tested with site-directed mutagenesis of Ser3.36(159) --> Ala and Ser3.36(159) --> Cys. The alanine substitution led to an 18-fold reduction in 5-HT affinity and the cysteine substitution to an intermediate 5-fold decrease. LSD affinity, in contrast, was unaffected by either mutation. N,N-Dimethyl 5-HT affinity was unaffected by the cysteine mutation and had a comparatively small 3-fold decrease in affinity for the alanine mutant. These findings identify a mode of ligand-receptor complexation that involves two receptor side chains interacting with the same functional group of specific serotonergic ligands. This interaction serves to orient the ligands in the binding pocket and may influence the degree of receptor activation. PMID:8663249

  14. Cerebral circulatory and metabolic effects of 5-hydroxytryptamine in anesthetized baboons.

    PubMed Central

    Harper, M A; MacKenzie, E T

    1977-01-01

    1. The cerebral circulatory effects of the intracarotid administration of 5-hydroxytryptamine were examined in anaesthetized baboons. Cerebral blood flow was measured by the intracarotid 133Xe technique, cerebral O2 consumption and glucose uptake were measured as indices of brain metabolism and electrocortical activity was continuously monitored. 2. Despite a marked reduction in the calibre of the internal carotid artery (assessed angiographically), the intracarotid infusion of 5-hydroxytryptamine 0-1 microgram/kg. min did not effect any significant changes in cerebral blood flow, O2 consumption or glucose uptake. 3. Following transient osmotic disruption of the blood-brain barrier with the intracarotid infusion of hypertonic urea, the same dose of 5-hydroxytryptamine effected a marked reduction in cerebral blood flow from 51 +/- 2 to 36 +/- 2 ml./100 g. min (mean +/- S.E.; P less than 0-01). Both indices of cerebral metabolism were reduced significantly and the e.e.g. showed a more pronounced suppression-burst pattern. 4. We postulate that the cerebral circulatory responses to 5-hydroxytryptamine are dependent upon the integrity of the blood-brain barrier and the predominant effect of the intravascular administration of 5-hydroxytryptamine is on cortical activity or metabolism, rather than on cerebrovascular smooth muscle. Images Plate 1 PMID:411921

  15. The major role of peripheral release of histamine and 5-hydroxytryptamine in formalin-induced nociception.

    PubMed

    Parada, C A; Tambeli, C H; Cunha, F Q; Ferreira, S H

    2001-01-01

    Formalin injected subcutaneously into the paw is a widely used model of pain. This procedure evokes a short-lasting period of flinching (phase 1) and a long-lasting period of intense flinching (phase 2) following a very short period of quiescence. Phase 2 has been extensively used to support the involvement of central (spinal cord) sensitization in inflammatory hyperalgesia. The present study evaluated the contribution of stimulation of peripheral nociceptors by the release of endogenous mediators at the site of lesion. The participation of histamine and 5-hydroxytryptamine was demonstrated by the treatment of the rat hindpaws with selective histamine H1 (pyrilamine and meclizine) and histamine H2 (cimetidine) receptor antagonists or selective 5-hydroxytryptamine(1A) (WAY100,135) and 5-hydroxytryptamine(4/3) (tropisetron) receptor antagonists. The co-administration of pyrilamine or meclizine with formalin (1%) significantly reduced phases 1 and 2, while cimetidine had no effect. Pyrilamine administration during the period of quiescence (10min after formalin administration) caused strong dose-related inhibition of phase 2. The co-administration of tropisetron with formalin caused a blockade of both phases, while with WAY100,135 caused only inhibition of the phase 2. In contrast, tropisetron administrated during the period of quiescence did not cause antinociception. Histamine and 5-hydroxytryptamine receptors could be strongly activated in naïve animals by administration of a mixture of both agonists or compound 48/80 (2microg/paw) which is known to release both mediators from mast cells. Pretreatment of the paws with a mast cell stabilizer, sodium cromoglycate, significantly reduced the second phase of the formalin injection model. From these results we suggest that phases 1 and 2 of the formalin test are dependent upon the ongoing afferent input. Furthermore, while histamine H1 participates in both phases, 5-hydroxytryptamine(4/3) participates in phase 1 and 5

  16. Cholestasis of pregnancy, pruritus and 5-hydroxytryptamine 3 receptor antagonists.

    PubMed

    Schumann, Roman; Hudcova, Jana

    2004-09-01

    Pruritus, an early symptom of intrahepatic cholestasis of pregnancy, may be severe. Conventional treatment includes ursodeoxycholic acid and cholestyramine. Ondansetron, a 5-hydroxytryptamine 3 receptor antagonist antiemetic, has been shown to reduce pruritus of different etiologies including cholestasis. We now report the successful preoperative use of ondansetron in a patient with pruritus from intrahepatic cholestasis of pregnancy. While the mechanism for our patient's response is poorly understood, 5-hydroxytryptamine 3 receptor antagonists should be further evaluated and possibly considered as a treatment option for intrahepatic cholestasis of pregnancy-related pruritus. PMID:15315599

  17. Increase of 5-hydroxytryptamine in the rat brain by raunescine

    PubMed Central

    Paasonen, M. K.; Kärki, N. T.

    1959-01-01

    The Rauwolfia alkaloid raunescine (5 mg./kg., intraperitoneally) increased the concentration of 5-hydroxytryptamine in the brains of rats after iproniazid pre-treatment. This was evident 3 to 4 hr. after raunescine administration. There was no general increase in the noradrenaline content of the brains. In the intestine, raunescine depleted the 5-hydroxytryptamine content by about 50% within 3 to 4 hr. if the animals had been pre-treated with iproniazid. Iproniazid did not increase the content of noradrenaline in the intestine. PMID:13662567

  18. Voltammetric detection of 5-hydroxytryptamine release in the rat brain.

    PubMed

    Hashemi, Parastoo; Dankoski, Elyse C; Petrovic, Jelena; Keithley, Richard B; Wightman, R M

    2009-11-15

    5-Hydroxytryptamine (5-HT) is an important molecule in the brain that is implicated in mood and emotional processes. In vivo, its dynamic release and uptake kinetics are poorly understood due to a lack of analytical techniques for its rapid measurement. Whereas fast-scan cyclic voltammetry with carbon fiber microelectrodes is used frequently to monitor subsecond dopamine release in freely moving and anesthetized rats, the electrooxidation of 5-HT forms products that quickly polymerize and irreversibly coat the carbon electrode surface. Previously described modifications of the electrochemical waveform allow stable and sensitive 5-HT measurements in mammalian tissue slice preparations and in the brain of fruit fly larvae. For in vivo applications in mammals, however, the problem of electrode deterioration persists. We identify the root of this problem to be fouling by extracellular metabolites such as 5-hydoxyindole acetic acid (5-HIAA), which is present in 200-1000 times the concentration of 5-HT and displays similar electrochemical properties, including filming of the electrode surface. To impede access of the 5-HIAA to the electrode surface, a thin layer of Nafion, a cation exchange polymer, has been electrodeposited onto cylindrical carbon-fiber microelectrodes. The presence of the Nafion film was confirmed with environmental scanning electron microscopy and was demonstrated by the diminution of the voltammetric signals for 5-HIAA as well as other common anionic species. The modified microelectrodes also display increased sensitivity to 5-HT, yielding a characteristic cyclic voltammogram that is easily distinguishable from other common electroactive brain species. The thickness of the Nafion coating and a diffusion coefficient (D) in the film for 5-HT were evaluated by measuring permeation through Nafion. In vivo, we used physiological, anatomical, and pharmacological evidence to validate the signal as 5-HT. Using Nafion-modified microelectrodes, we present the

  19. Distribution of 125I-galanin binding sites, immunoreactive galanin, and its coexistence with 5-hydroxytryptamine in the cat spinal cord: Biochemical, histochemical, and experimental studies at the light and electron microscopic level

    SciTech Connect

    Arvidsson, U.; Ulfhake, B.; Cullheim, S.; Bergstrand, A.; Theodorson, E.; Hoekfelt, T. )

    1991-06-01

    The distribution of galanin-like immunoreactivity (GAL-LI) in the spinal cord of the cat was studied by use of indirect histochemistry and the peroxidase-antiperoxidase (PAP) technique. In the ventral horn GAL-immunoreactive (IR) axonal fibers and terminals were most frequent in the ventral part of the motor nucleus. The GAL-IR axons also contained 5-hydroxytryptamine (5-HT)-LI, and they disappeared after spinal cord transection. It was concluded that these GAL-IR fibers belong to the serotoninergic bublospinal pathway. In the medulla oblongata from normal cats, scattered GAL-IR cell bodies were encountered within the nucleus raphe obscurus and nucleus raphe pallidus. Electron microscopic observations revealed that the fine structure of the GAL-IR axonal boutons in the motor nucleus was similar to that of 5-HT-IR boutons with a varying number of immunoreactive large dense core vesicles. The postsynaptic element in all cases studied was a dendrite. A dense GAL-IR axonal plexus was found in the superficial laminae I-II of the dorsal horn. Coexistence was found between the GAL- and substance P-LI in fibers within the dorsal horn plexus. Spinal cord transection did not alter the pattern of GAL-LI in the dorsal horn, while the vast majority of GAL-IR axonal swellings disappeared following dorsal root sectioning. Electron microscopic observations in lamina II (substantia gelatinosa) revealed that the GAL-IR axonal terminals could be divided into two main groups. One with small to medium-sized axonal boutons formed synaptic contacts with both dendritic and axonal profiles. The other formed the central axon terminals of glomeruli, suggesting that GAL-LI may be present in C-type primary afferents. Numerous small GAL-IR cell bodies were encountered in laminae II and III. GAL-IR cell bodies were also observed in lamina X.

  20. Anticonvulsant compounds and 5-hydroxytryptamine in rat brain

    PubMed Central

    Bonnycastle, D. D.; Giarman, N. J.; Paasonen, M. K.

    1957-01-01

    In rats, a series of anticonvulsant compounds have been shown to cause a significant elevation of brain 5-hydroxytryptamine (5-HT) levels in comparison with control values. This increase in 5-HT only occurred in brain tissue and was not observed in spleen, upper small intestine or blood. Elevation of brain levels of 5-HT by iproniazid (Marsilid) or 5-hydroxytryptophan failed to give protection against the convulsant or lethal action of lept zol (75 mg./kg.). PMID:13446378

  1. 5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials

    PubMed Central

    Pithadia, Anand B.; Jain, Sunita M.

    2009-01-01

    5-hydroxytryptamine (5-HT) has become one of the most investigated and complex biogenic amines. The main receptors and their subtypes, e.g., 5-HTI (5-HT1A, 5-HT1B, 5-HTID, 5-HTIE and 5-HT1F), 5-HT2 (5-HT2A, 5-HT2B and 5-HT2C), 5-HT3, 5-HT4, 5-HT5 (5-HT5A, 5-HT5B), 5-HT6 and 5-HT7 have been identified. Specific drugs which are capable of either selectively stimulating or inhibiting these receptor subtypes are being designed. This has generated therapeutic potentials of 5-HT receptor modulators in a variety of disease conditions. Conditions where 5-HT receptor modulators have established their use with distinct efficacy and advantages include migraine, anxiety, psychosis, obesity and cancer therapy-induced vomiting by cytotoxic drugs and radiation. Discovery of 5-HT, its biosynthesis, metabolism, physiological role and the potential of 5-HT receptor modulators in various nervous, cardiovascular and gastrointestinal tract disorders, bone growth and micturition have been discussed in this article. Keywords 5-hydroxytryptamine (5-HT) receptors; Modulators; Biogenic amines PMID:22505971

  2. 5-Hydroxytryptamine (5-HT) Cellular Sequestration during Chronic Exposure Delays 5-HT3 Receptor Resensitization due to Its Subsequent Release*

    PubMed Central

    Hothersall, J. Daniel; Alexander, Amy; Samson, Andrew J.; Moffat, Christopher; Bollan, Karen A.; Connolly, Christopher N.

    2014-01-01

    The serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT3) receptors. We report that recombinantly expressed 5-HT3 receptor binding sites are reduced by chronic exposure to 5-HT (IC50 of 154.0 ± 45.7 μm, t½ = 28.6 min). This is confirmed for 5-HT3 receptor-induced contractions in the guinea pig ileum, which are down-regulated after chronic, but not acute, exposure to 5-HT. The loss of receptor function does not involve endocytosis, and surface receptor levels are unaltered. The rate and extent of down-regulation is potentiated by serotonin transporter function (IC50 of 2.3 ± 1.0 μm, t½ = 3.4 min). Interestingly, the level of 5-HT uptake correlates with the extent of down-regulation. Using TX-114 extraction, we find that accumulated 5-HT remains soluble and not membrane-bound. This cytoplasmically sequestered 5-HT is readily releasable from both COS-7 cells and the guinea pig ileum. Moreover, the 5-HT level released is sufficient to prevent recovery from receptor desensitization in the guinea pig ileum. Together, these findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization. PMID:25281748

  3. 5-Hydroxytryptamine and dopamine transport by rat and human blood platelets

    PubMed Central

    Gordon, J.L.; Olverman, H.J.

    1978-01-01

    1 Uptake of 5-hydroxytryptamine (5-HT) by rat platelets in plasma was very rapid and diffusion did not contribute significantly at substrate concentrations that did not saturate the active transport. 2 Under conditions which allowed measurement of initial rates of uptake, kinetic analysis revealed a high affinity uptake mechanism for 5-HT (Km = 0.7 μM). 3 Uptake of dopamine was relatively slow and involved a lower affinity (Km = 70 μM) active transport process. Diffusion contributed significantly at concentrations that did not saturate the active transport. 4 5-HT competitively inhibited uptake of dopamine, and vice versa; Ki values for both amines were similar to their respective Km values for uptake. 5 Chlorimipramine, desmethylimipramine and benztropine were tested as uptake inhibitors. Each was equipotent against 5-HT and dopamine, although the absolute potency of the drugs varied greatly. Chlorimipramine was the most potent (Ki## 100 nM), and kinetic analysis revealed that the inhibition was competitive against both 5-HT and dopamine. 6 Similar results were obtained in studies with human platelets: Km values for 5-HT and dopamine were about 1 μM and 100 μM respectively. Activity profiles of inhibitors were also similar: each compound tested was equipotent against 5-HT and dopamine, and the two amines each competitively inhibited uptake of the other. 7 We conclude that dopamine is actively transported by platelets via the 5-HT uptake mechanism, but with a much lower affinity. There is no high-affinity dopamine-specific mechanism corresponding to that in the corpus striatum. Consequently although platelets may be valid models of transport in 5-hydroxytryptaminergic neurones, they should not be regarded as models for the dopamine transport mechanism found in dopaminergic neurones. PMID:623937

  4. 5-hydroxytryptamine medications for the treatment of obesity.

    PubMed

    Burke, L K; Heisler, L K

    2015-06-01

    The central 5-hydroxytryptamine (5-HT; serotonin) system represents a fundamental component of the brain's control of energy homeostasis. Medications targeting the 5-HT pathway have been at the forefront of obesity treatment for the past 15 years. Pharmacological agents targeting 5-HT receptors (5-HTR), in combination with genetic models of 5-HTR manipulation, have uncovered a role for specific 5-HTRs in energy balance and reveal the 5-HT2 C R as the principal 5-HTR mediating this homeostatic process. Capitalising on this neurophysiological machinery, 5-HT2 C R agonists improve obesity and glycaemic control in patient populations. The underlying therapeutic mechanism has been probed using model systems and appears to be achieved primarily through 5-HT2 C R modulation of the brain melanocortin circuit via activation of pro-opiomelanocortin neurones signalling at melanocortin4 receptors. Thus, 5-HT2 C R agonists offer a means to improve obesity and type 2 diabetes, which are conditions that now represent global challenges to human health. PMID:25925636

  5. 5-hydroxytryptamine induced relaxation in the pig urinary bladder neck

    PubMed Central

    Recio, Paz; Barahona, María Victoria; Orensanz, Luis M; Bustamante, Salvador; Martínez, Ana Cristina; Benedito, Sara; García-Sacristán, Albino; Prieto, Dolores; Hernández, Medardo

    2009-01-01

    Background and purpose 5-Hydroxytryptamine (5-HT) is one of the inhibitory mediators in the urinary bladder outlet region. Here we investigated mechanisms involved in 5-HT-induced relaxations of the pig bladder neck. Experimental approach Urothelium-denuded strips of pig bladder were mounted in organ baths for isometric force recordings of responses to 5-HT and electrical field stimulation (EFS). Key results After phenylephrine-induced contraction, 5-HT and 5-HT receptor agonists concentration-dependently relaxed the preparations, with the potency order: 5-carboxamidotryptamine (5-CT) > 5-HT = RS67333 > (±)-8-hydroxy-2-dipropylaminotetralinhydrobromide > m-chlorophenylbiguanide > α-methyl-5-HT > ergotamine. 5-HT and 5-CT relaxations were reduced by the 5-HT7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulphonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride and potentiated by (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide dihydrochloride (WAY 100135) and cyanopindolol, 5-HT1A and 5-HT1A/1B receptor antagonists respectively. Inhibitors of 5-HT1B/1D, 5-HT2, 5-HT2B/2C, 5-HT3, 5-HT4, 5-HT5A and 5-HT6 receptors failed to modify 5-HT responses. Blockade of monoamine oxidase A/B, noradrenergic neurotransmission, α-adrenoceptors, muscarinic and purinergic receptors, nitric oxide synthase, guanylate cyclase and prostanoid synthesis did not alter relaxations to 5-HT. Inhibitors of Ca2+-activated K+ and ATP-dependent K+ channels failed to modify 5-HT responses but blockade of neuronal voltage-gated Na+-, Ca2+-and voltage-gated K+ (Kv)-channels potentiated these relaxations. Adenylyl cyclase activation and cAMP-dependent protein kinase (PKA) inhibition potentiated and reduced, respectively, 5-HT-induced responses. Under non-adrenergic, non-cholinergic, non-nitrergic conditions, EFS induced neurogenic, frequency-dependent, relaxations which were resistant to WAY 100135 and cyanopindolol. Conclusions and implications 5-HT relaxed

  6. Naftopidil inhibits 5-hydroxytryptamine-induced bladder contraction in rats.

    PubMed

    Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

    2013-01-30

    Naftopidil is an α(1D) and α(1A) subtype-selective α(1)-adrenoceptor antagonist that has been used to treat lower urinary tract symptoms of benign prostatic hyperplasia. In this study, we investigated the effects of naftopidil on 5-hydroxytryptamine (5-HT)-induced rat bladder contraction (10(-8)-10(-4) M). Naftopidil (0.3, 1, and 3 μM) inhibited 5-HT-induced bladder contraction in a concentration-dependent manner. On the other hand, other α(1)-adrenoceptor antagonists, tamsulosin, silodosin or prazosin, did not inhibit 5-HT-induced bladder contraction. The 5-HT-induced bladder contraction was inhibited by both ketanserin and 4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine (RS127445), serotonin 5-HT(2A) and 5-HT(2B) receptor antagonists, respectively. In addition, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and α-methyl-5-HT, 5-HT(2A) and 5-HT(2) receptor agonists, respectively, induced bladder contraction. The 5-HT-induced bladder contraction was not inhibited by N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide (WAY-100635), [1-[2[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate (GR113808) or (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulphonyl]phenol (SB269970), 5-HT(1A), 5-HT(4) and 5-HT(7) receptor antagonists, respectively. Naftopidil inhibited both the 5-HT(2A) and 5-HT(2) receptor agonists-induced bladder contractions. Naftopidil binds to the human 5-HT(2A) and 5-HT(2B) receptors with pKi values of 6.55 and 7.82, respectively. These results suggest that naftopidil inhibits 5-HT-induced bladder contraction via blockade of the 5-HT(2A) and 5-HT(2B) receptors in rats. Furthermore, 5-HT-induced bladder contraction was enhanced in bladder strips obtained from bladder outlet obstructed rats, with this contraction inhibited by naftopidil. The beneficial effects of naftopidil on storage symptoms such as urinary frequency and nocturia in patients with benign

  7. Excitation and depression of cortical neurones by 5-hydroxytryptamine

    PubMed Central

    Roberts, M. H. T.; Straughan, D. W.

    1967-01-01

    1. 5-Hydroxytryptamine (5-HT) and various 5-HT antagonists have been applied micro-electrophoretically from multibarrelled micropipettes into the environment of single neurones in the post-sigmoid and suprasylvian gyri of the cat cerebral cortex. 2. In unanaesthetized animals (encéphale isolé) a high proportion of neurones (30%) were excited by 5-HT. This excitation usually had a rapid onset and was seen both in spontaneously active neurones and in otherwise quiescent neurones in which firing was induced by L-glutamate. Some neurones were so sensitive that the uncontrolled diffusion from micropipettes was sufficient to excite them. More cells were excited by 5-HT applied as a cation from solutions of the bimaleate salt than when solutions of the creatinine sulphate salt were used. 3. In a high proportion of cells (33%) spontaneous firing or amino acid excitation was depressed by 5-HT. 4. A mixed effect was seen in a small proportion (6%) of the cells tested; usually 5-HT caused an excitation initially which was followed by a depression. In other cells, desensitization occurred, and the excitatory effect of 5-HT was diminished or lost. 5. When glutamate was used to excite otherwise quiescent cells, there was a significant increase in the number of cells excited by 5-HT and a significant decrease in the number of cells unaffected compared with spontaneously active cells. 6. The micro-electrophoretic application of D-lysergic diethylamide (LSD 25), 2-brom LSD (BOL 148), methysergide (UML 491), or 2′- (3-dimethylaminopropylthio)cinnamanilide (SQ 10643) temporarily prevented excitation by 5-HT in half the cells tested. LSD and SQ 10643 were particularly potent in this respect. This antagonism of 5-HT excitation could still be seen when excitation of the cell by L-glutamate or acetylcholine (ACh) was unaffected. 7. The depression induced by 5-HT was not prevented by the application of known 5-HT antagonists in the majority of the cells tested (93%). In two cells

  8. Loss of 5-hydroxytryptamine from mammalian circulating labelled platelets

    PubMed Central

    Osim, E. E.; Wyllie, J. H.

    1983-01-01

    1. Platelets were obtained from three species of animal: rats, rabbits and dogs. They were labelled with 111In oxine to tag individual platelets and with 14C-labelled 5-hydroxytryptamine (5-HT). Doubly labelled platelets from rabbits and dogs were returned to their donors; in the case of rats the platelets were injected intravenously into other, identical rats. At time intervals from 2 to 64 hr, blood samples were drawn and platelets were collected. 111In and 14C were separately counted. In some experiments animals received the 5-HT precursor, 5-hydroxytryptophan (5-HTP) I.P. (for rats and rabbits) or subcutaneously (for dogs) in a dose of 20 mg/kg daily to accelerate synthesis of 5-HT. 2. 111In disappeared in approximately an exponential fashion in all experiments and the rate of disappearance was not affected by treatment with 5-HTP. The half-life for 111In in four control rats was 18·7 hr and in five rats treated with 5-HTP was 17·8 hr. In rabbits the half-life was 20·4 hr for eight control and 21·2 hr for seven treated with 5-HTP. In the dogs the half-life was 21·0 hr for control and 27·7 hr for experiments with 5-HTP. In control rats, the 14C behaved like the 111In. However, in control rabbits the half-life for 14C was 38·0 hr which is significantly longer than for 111In (P < 0·005). 14C also disappeared more slowly than the 111In in the dogs. 3. In all species treatment with 5-HTP accelerated the disappearance of the 14C approximately three-fold. This was not a reserpine-like effect because the platelets contained more, not less 5-HT than usual. 4. In an attempt to discover the fate of 5-HT disappearing from circulating platelets, experiments were made in which platelets from one rat were doubly labelled, and were then injected into two other rats from the identical strain; one of the recipients received daily I.P. injections of 20 mg/kg of 5-HTP. The other rat in each pair acted as a control. 5. Results from twelve control rats showed that the 14C

  9. Localized Release of Serotonin (5-Hydroxytryptamine) by a Fecal Pellet Regulates Migrating Motor Complexes in Murine Colon

    PubMed Central

    HEREDIA, DANTE J.; DICKSON, EAMONN J.; BAYGUINOV, PETER O.; HENNIG, GRANT W.; SMITH, TERENCE K.

    2009-01-01

    Background & Aims The colonic migrating motor complex (CMMC) is a motor pattern that regulates the movement of fecal matter, through a rhythmic sequence of electrical activity and/or contractions, along the large bowel. CMMCs have largely been studied in empty preparations; we investigated whether local reflexes generated by a fecal pellet modify the CMMC to initiate propulsive activity. Methods Recordings of CMMCs were made from the isolated murine large bowel, with or without a fecal pellet. Transducers were placed along the colon to record muscle tension and propulsive force on the pellet and microelectrodes were used to record electrical activity from circular muscle cells anal and oral of a pellet and in colons without the mucosa. Results Spontaneous CMMCs propagated in both an oral or anal direction. When a pellet was inserted, CMMCs increased in frequency and propagated anally, exerting propulsive force on the pellet. The amplitude of slow waves increased during the CMMC. Localized mucosal stimulation/circumferential stretch evoked a CMMC, regardless of stimulus strength. The serotonin (5-hydroxytryptamine-3) antagonist ondansetron reduced the amplitude of the CMMC, the propulsive force on the pellet, and the response to mucosal stroking, but increased the apparent conduction velocity of the CMMC. Removing the mucosa abolished spontaneous CMMCs, which still could be evoked by electrical stimulation. Conclusions The fecal pellet activates local mucosal reflexes, which release serotonin (5-hydroxytryptamine) from enterochromaffin cells, and stretch reflexes that determine the site of origin and propagation of the CMMC, facilitating propulsion. PMID:19138686

  10. Effect of Y-25130, a selective 5-hydroxytryptamine3 receptor antagonist, on gastric emptying in mice.

    PubMed

    Haga, K; Asano, K; Inaba, K; Morimoto, Y; Setoguchi, M

    1994-01-01

    The effect of Y-25130 on gastric emptying of nutrient test meals (solid chow) was examined in mice. In a dose range of 0.01-1 mg/kg, p.o., Y-25130 significantly accelerated gastric emptying of solid meals in a dose-dependent manner, at an ED30 of 0.021 mg/kg. Other 5-hydroxytryptamine3 receptor antagonists and prokinetic agents having 5-hydroxytryptamine3 receptor antagonistic properties accelerated the emptying of solid meals in the following rank order of potency: Y-25130 = granisetron > or = tropisetron > ondansetron > cisapride > metoclopramide. The acceleration of the gastric emptying showed a good correlation with the antagonistic potencies of these compounds on 5-hydroxytryptamine3 receptors, determined by the inhibition test of the von Bezold-Jarisch reflex in anesthetized rats (r2 = 0.99). Domperidone (1 and 10 mg/kg, p.o.) and trimebutine (10 and 100 mg/kg, p.o.) failed to increase the rate of emptying from the stomach. Cisplatin (30 mg/kg, i.p.), a chemotherapeutic agent, significantly delayed the gastric emptying of solid meals, and Y-25130 (0.1-1 mg/kg, p.o.) prevented such a delay in emptying in a dose-dependent manner. These results suggest that Y-25130 accelerates the gastric emptying in mice by antagonism of the 5-hydroxytryptamine3 receptor. PMID:7625886

  11. Peptide displacement of ( sup 3 H)5-hydroxytryptamine binding to bovine cortical membranes

    SciTech Connect

    Takeuchi, Y.; Root-Bernstein, R.S.; Shih, J.C. )

    1990-12-01

    Chemical studies have demonstrated that peptides such as the encephalitogenic (EAE) peptide of myelin basic protein (MBP) and luteinizing hormone-releasing hormone (LHRH) can bind serotonin (5-hydroxytryptamine, 5-HT) in vitro. The present research was undertaken to determine whether such binding interferes with 5-HT binding to its 5-HT1 receptors on bovine cerebral cortical membranes. EAE peptide and LHRH displaced ({sup 3}H)5-HT with IC50s of 4.0 x 10(-4) and 1.8 x 10(-3) M respectively. MBP itself also showed apparent displacing ability with an IC50 of 6.0 x 10(-5) M, though it also caused aggregation of cortical membranes that might have interfered with normal receptor binding. These results support previous suggestions that the tryptophan peptide region of MBP may act as a 5-HT receptor in the neural system. We also tested the effects of muramyl dipeptide (N-acetyl-muramyl-L-Ala-D-isoGln, MD), a bacterial cell-wall breakdown product that acts as a slow-wave sleep promoter, binds to LHRH and EAE peptide, and competes for 5-HT binding sites on macrophages. It showed no significant displacement of 5-HT binding to cortical membranes (IC50 greater than 10(-1) M), but its D-Ala analogue did (IC50 = 1.7 x 10(-3) M). Thus, it seems likely that the 5-HT-related effects of naturally occurring muramyl peptides are physiologically limited by receptor types.

  12. Circadian variation in sensitivity of suprachiasmatic and lateral geniculate neurones to 5-hydroxytryptamine in the rat.

    PubMed Central

    Mason, R

    1986-01-01

    Extracellular single-unit recordings were obtained from neurones in the suprachiasmatic nuclei (s.c.n.) of the rat (a putative circadian pace-maker), the ventral lateral geniculate nucleus (v.l.g.n.) and the hippocampus. These areas receive a 5-hydroxytryptamine (5-HT) innervation from the raphe nuclei. Recording of neuronal activity in the s.c.n., v.l.g.n. and the hippocampus revealed a diurnal variation in the response to the ionophoresis of 5-HT. This variation was manifest as a 2-3-fold increase in post-synaptic sensitivity to 5-HT during the subjective dark (active) phase of the circadian cycle. In contrast there was no apparent circadian variation in the sensitivity of s.c.n., v.l.g.n. or hippocampal neurones to ionophoresed gamma-aminobutyric acid (GABA). Neuronal activity recorded in the s.c.n., v.l.g.n. and hippocampus also exhibited a circadian variation in the recovery from 5-HT-induced suppression of firing. This may reflect reuptake processes as recovery can be prolonged by ionophoresis of uptake blockers (imipramine or fluoxetine). Rats (n = 15) expressing circadian arrhythmicity in their rest-activity behaviour induced by long-term continuous illumination (150-200 lx) showed no apparent circadian variation in 5-HT sensitivity. This loss was accompanied by either the development of a 5-6-fold subsensitivity to ionophoresed 5-HT (eleven out of fifteen rats) or a 2-3-fold supersensitivity to ionophoresed 5-HT (four out of fifteen rats). A similar loss of circadian variation and the development of a subsensitivity to ionophoresed 5-HT was also found in three rats sustaining complete electrolytic lesions of the s.c.n. These changes were not found in rats (n = 4) with partial s.c.n. lesions. These results implicate the s.c.n., or fibres passing through it, in the circadian modulation of 5-HT sensitivity in neurones both intrinsic to the s.c.n. circadian pace-maker itself and in the hippocampus and lateral geniculate nucleus (regions remote from the s

  13. Release of ( sup 14 C)5-hydroxytryptamine from human platelets by red wine

    SciTech Connect

    Jarman, J.; Glover, V.; Sandler, M. )

    1991-01-01

    Red wine, at a final dilution of 1/50, caused released of ({sup 14}C)5-hydroxytryptamine (5-HT) from preloaded platelets, an effect which was not observed with any white wines or beers tested. Since 5-HT, is probably released from body stores during migraine attacks and red wine is known to provoke migraine episodes in susceptible individuals, release of 5-HT, possibly from central stores, could represent a plausible mechanism for its mode of action.

  14. Effects on amine oxidase of substances which antagonize 5-hydroxytryptamine more than tryptamine on the rat fundus strip

    PubMed Central

    Barlow, R. B.

    1961-01-01

    Certain substances, 2-bromolysergic acid diethylamide, dimethyltryptamine (3-(2-dimethylaminoethyl)indole), 2-methyldimethyltryptamine (3-(2-dimethylaminoethyl)-2-methylindole), and 5-benzyloxydimethyltryptamine (5-benzyloxy-3-(2-dimethylaminoethyl)indole), antagonize the effects of 5-hydroxytryptamine on the rat fundus strip more than those of tryptamine. These substances have been tested for their ability to inhibit the oxidation of tryptamine and 5-hydroxytryptamine by suspensions of guinea-pig liver and rat fundus. 2-Bromolysergic acid diethylamide has virtually no inhibitory activity and it is doubtful if the others produce any significant inhibition of amine oxidase in the concentrations which antagonize the effects of 5-hydroxytryptamine more than those of tryptamine. It seems that the differential character of the blocking action of these compounds should be ascribed either to interference with the transport of tryptamine (but not 5-hydroxytryptamine) through the cell wall, coupled with the block of a receptor common to both tryptamine and 5-hydroxytryptamine, or to the existence of separate tryptamine and 5-hydroxytryptamine receptors. The amine oxidases of the guinea-pig liver and rat fundus appear to be a mixture of at least two types of enzyme, one of which has a higher affinity for 5-hydroxytryptamine than the other and is more susceptible to inhibition by 2-methyldimethyltryptamine. PMID:13687054

  15. The effect of atropine on the activation of 5-hydroxytryptamine3 channels in rat nodose ganglion neurons.

    PubMed

    Fan, P; Weight, F F

    1994-10-01

    It has been suggested that changes in brain 5-hydroxytryptamine3 receptor function may contribute to some behavior disorders, such as anxiety, schizophrenia and drug abuse. We are using the whole-cell version of the patch-clamp technique to study the function of 5-hydroxytryptamine3 channels in neurons freshly dissociated from rat nodose ganglion. In these cells, 5-hydroxytryptamine elicits an inward current over the concentration range of 0.25-100 microM (EC50 = 2.62 microM) by activating 5-hydroxytryptamine3 receptors. The muscarinic cholinergic antagonist atropine reduced the amplitude of 5-hydroxytryptamine activated inward current in a concentration-dependent manner. Other muscarinic antagonists, scopolamine, dexetimide, the M1 muscarinic receptor antagonist pirenzepine, the M2 receptor antagonist methoctramine and the M3 receptor antagonist 4-DAMP methiodide also inhibited 5-hydroxytryptamine-induced inward current. Atropine did not appear to change the reversal potential of this current. In the presence of 5 microM atropine, the concentration-response curve for 5-hydroxytryptamine current was shifted to the right in a parallel fashion. The EC50 value for 5-hydroxytryptamine was increased from 2.62 to 8.76 microM. Schild plots of increasing atropine and 5-hydroxytryptamine concentrations revealed a pA2 value of 5.74 for atropine (apparent KD = 1.8 microM). These observations suggest that atropine competitively antagonizes the activation of a receptor for the neurotransmitter serotonin, a novel action of muscarinic antagonists in the nervous system. This effect of atropine may contribute to the clinical symptoms seen in severe atropine intoxication. PMID:7531305

  16. Role of 5-hydroxytryptamine in platelet thrombus formation and mechanisms of inhibition of thrombus formation by 5-hydroxytryptamine2A antagonists in rabbits.

    PubMed

    Takano, S

    1995-01-01

    The role of 5-hydroxytryptamine (5-HT) in platelet thrombus formation and in the mechanisms of inhibition of thrombus formation by 5-HT2A antagonists was investigated using a turbidimetric method. Collagen-induced platelet aggregation occurred simultaneously with a release of 5-HT from the platelets. The supernatant of collagen-aggregated platelets induced a further aggregation volume-dependently. This supernatant-induced aggregation was inhibited by either 5-HT2A antagonists or adenosine-diphosphate (ADP) scavenging. 5-Hydroxytryptamine and a small amount of the supernatant shifted the dose-response curves of collagen to the left. The aggregation velocity and the onset of aggregation by collagen were significantly increased by the supernatant, but not by 5-HT. The 5-HT2A antagonists, ketanserin and MCI-9042, returned the dose-response curves of the maximum aggregation and of the aggregation velocity of collagen, which were already amplified by the supernatant, to the original values. The onset of aggregation was delayed by the antagonists, but was not completely returned to the original points. There were distinct differences between the effects of endogenous 5-HT, derived from platelets which were stimulated by collagen, and those of exogenous 5-HT on both extensive platelet activation and amplification of the collagen-induced aggregation. These findings suggest that endogenous 5-HT activates platelets in synergism with ADP. The 5-HT2A antagonists used, block the synergism via 5-HT2A receptors and lead to inhibition of a positive feedback loop of thrombus formation. PMID:8836449

  17. Influence of 5-hydroxytryptamine (serotonin) on blood flow in the dog pulp

    SciTech Connect

    Kim, S.; Trowbridge, H.O.; Dorscher-Kim, J.E.

    1986-05-01

    The effect of intra-arterial injection of 5-hydroxytryptamine (5-HT) on pulpal blood flow of the dog was determined using the 15-micron radioisotope-labeled microsphere injection method. Pulpal blood flow was significantly reduced following the 5-HT injection. This decrease in blood flow appeared to be due to vasoconstriction as determined by an increase in pulpal vascular hindrance. However, our findings do not preclude the possibility that blood flow was reduced as a result of passive compression of venules produced by vasodilation in a low-compliance environment.

  18. The release of nucleotides, 5-hydroxytryptamine and enzymes from human blood platelets during aggregation

    PubMed Central

    Mills, D. C. B.; Robb, I. A.; Roberts, G. C. K.

    1968-01-01

    1. Adenosine diphosphate (ADP) and adrenaline caused the aggregation of human platelets suspended in plasma containing citrate anticoagulant and stirred at 37° C. The aggregation occurred in two phases and the second phase was associated with the appearance in the plasma of up to 30% of the ATP and 55% of the ADP present in the platelets. The concentration of ADP appearing in the plasma was up to 7 times the concentration added. 2. Radioactivity was released by ADP and by adrenaline from platelets labelled with radioactive 5-hydroxytryptamine; this release was closely correlated with the second phase of aggregation and with the release of nucleotides. 3. Acid phosphatase, β-glucuronidase and adenylate kinase were released to a small extent during second phase aggregation by ADP or adrenaline; thrombin and collagen particles caused significantly greater release of β-glucuronidase than of either acid phosphatase or of adenylate kinase. 4. Morphological changes indicating degranulation of the platelets were observed during the second phase of aggregation produced by adrenaline and by ADP. 5. The second phase of aggregation, degranulation of platelets, and the release of nucleotides, of labelled 5-hydroxytryptamine and of enzymes, were all inhibited by concentrations of amitriptyline which did not inhibit aggregation. ImagesPlate 1Plate 2 PMID:5649642

  19. The effect of altered 5-hydroxytryptamine levels on beta-endorphin

    NASA Technical Reports Server (NTRS)

    Soliman, Karam F. A.; Mash, Deborah C.; Walker, Charles A.

    1986-01-01

    The purpose of the present study was to examine the effect of altering the concentration of 5-hydroxytryptamine (5-HT) on beta-endorphin (beta-Ep) content in the hypothalamus, thalamus, and periaqueductal gray (PAG)-rostral pons regions of the rat brain. The selective 5-HT reuptake inhibitor, fluoxetine (10 mg/kg), significantly lowered beta-Ep content in the hypothalamus and the PAG. Parachlorophenylalanine, which inhibits 5-HT synthesis, significantly elevated beta-Ep in all brain parts studied. Intracisternal injections of the neurotoxin 5-prime, 7-prime-dihydroxytryptamine with desmethylimipramine pretreatment significantly increased beta-Ep content in the hypothalamus and the PAG. In adrenalectomized rats, fluoxetine significantly decreased beta-Ep levels in the hypothalamus and increased the levels in the PAG. The results indicate that 5-HT may modulate the levels of brain beta-Ep.

  20. 5-hydroxytryptamine (5-HT) reduces total peripheral resistance during chronic infusion: direct arterial mesenteric relaxation is not involved

    PubMed Central

    2012-01-01

    Serotonin (5-hydroxytryptamine; 5-HT) delivered over 1 week results in a sustained fall in blood pressure in the sham and deoxycorticosterone acetate (DOCA)-salt rat. We hypothesized 5-HT lowers blood pressure through direct receptor-mediated vascular relaxation. In vivo, 5-HT reduced mean arterial pressure (MAP), increased heart rate, stroke volume, cardiac index, and reduced total peripheral resistance during a 1 week infusion of 5-HT (25 µg/kg/min) in the normotensive Sprague Dawley rat. The mesenteric vasculature was chosen as an ideal candidate for the site of 5-HT receptor mediated vascular relaxation given the high percentage of cardiac output the site receives. Real-time RT-PCR demonstrated that mRNA transcripts for the 5-HT2B, 5-HT1B, and 5-HT7 receptors are present in sham and DOCA-salt superior mesenteric arteries. Immunohistochemistry and Western blot validated the presence of the 5-HT2B, 5- HT1B and 5-HT7 receptor protein in sham and DOCA-salt superior mesenteric artery. Isometric contractile force was measured in endothelium-intact superior mesenteric artery and mesenteric resistance arteries in which the contractile 5- HT2A receptor was antagonized. Maximum concentrations of BW-723C86 (5- HT2B agonist), CP 93129 (5-HT1B agonist) or LP-44 (5-HT7 agonist) did not relax the superior mesenteric artery from DOCA-salt rats vs. vehicle. Additionally, 5-HT (10–9 M to 10–5 M) did not cause relaxation in either contracted mesenteric resistance arteries or superior mesenteric arteries from normotensive Sprague- Dawley rats. Thus, although 5-HT receptors known to mediate vascular relaxation are present in the superior mesenteric artery, they are not functional, and are therefore not likely involved in a 5-HT-induced fall in total peripheral resistance and MAP. PMID:22559843

  1. 5-Hydroxytryptamine-induced calcium-channel gating in rainbow trout (Oncorhynchus mykiss) peripheral blood lymphocytes.

    PubMed Central

    Ferriere, F; Khan, N A; Meyniel, J P; Deschaux, P

    1997-01-01

    The present study was conducted on peripheral blood lympho-cytes of rainbow trout (Oncorhynchus mykiss) to assess the role of 5-hydroxytryptamine (5-HT; 'serotonin') in calcium signalling. 5-HT-induced increases in intracellular free calcium concentrations, [Ca2+]i, and its action was mediated by 5-HT receptor subtype 3 (5-HT3), but not by 5-HT receptor subtype 1A (5-HT1A) or subtype 2 (5-HT2) in these cells. In Ca2+-containing medium (1 mM CaCl2), 5-HT and 2-methyl-5-HT (5-HT3 receptor agonist) induced increases in [Ca2+]i, whereas in Ca2+-free medium (0 Ca2+, 1 mM EGTA), these two agents failed to evoke increases in [Ca2+]i in these cells, demonstrating that 5-HT mobilizes Ca2+ from the extracellular environment. Furthermore, 5-HT-induced increases in [Ca2+]i are not contributed to by the intracellular endoplasmic reticulum (ER) pool, as thapsigargin, an agent that recruits Ca2+ from ER stores, had additive effects on 5-HT-induced [Ca2+]i responses in fish peripheral lymphocytes. 5-HT-induced increases in [Ca2+]i were mediated by 5-HT3 receptors via gating the calcium through L-type, but not N-type, calcium channels in trout lymphocytes. PMID:9173890

  2. 5-Hydroxytryptamine release from platelets by different red wines: implications for migraine.

    PubMed

    Pattichis, K; Louca, L L; Jarman, J; Sandler, M; Glover, V

    1995-01-13

    We have confirmed our earlier finding that most red wines are able to bring about 5-hydroxytryptamine (5-HT, serotonin) release from platelets in vitro. Platelets from individual subjects manifested varying degrees of releasing ability but responded to different wines with a similar rank ordering. There was a high correlation (r = 0.87) between the effect of red wine and that of reserpine in different individuals. Some types of red wine caused a consistently higher release of 5-HT than others in all subjects; one red wine in particular resulted in negligible release. When several brands of this 'low-releasing' red wine were further examined, they all showed a lower activity than all the brands of a 'high-releasing' red wine type. This variation in releasing power was not related to intensity of red colour. Partial purification of red wine was achieved by column chromatography and showed releasing activity to be associated with a low molecular weight orange fraction. Preliminary studies, using solid phase extraction methods, showed that the active components lie mainly in a subgroup of the flavonoid fraction. If any of the adverse effects of red wine, such as headache induction, derive from this 5-HT releasing ability, then it may be possible to prepare red wines free from the chemical substances responsible. PMID:7720790

  3. 5-Hydroxytryptamine antagonists and the 5-methoxy-N,N-dimethyltryptamine-induced changes of postdecapitation convulsions.

    PubMed

    Archer, T

    1987-01-01

    The ability of various compounds to antagonise the 5-MeODMT induced prolongations of latency and duration of postdecapitation convulsions (PDCs) were compared. The 5-hydroxytryptamine (5-HT) receptor antagonists, mianserin, methergoline, cinanserin and methysergide antagonised the 5-MeODMT (0.5 to 4.0 mg/kg) induced prolongations of latency to onset of convulsions substantially and to a lesser extent the prolongation of duration. The efficacy of the 5-HT antagonists for blocking 5-MeODMT changes of PDCs was roughly of the order mianserin greater than cinanserin greater than methysergide greater than methergoline. Pirenperone, the 5-HT2 antagonist, and pimozide, the dopamine receptor antagonist did not antagonise the 5-MeODMT induced changes. Mianserin, methergoline, cinanserin and methysergide, by themselves, prolonged the duration of PDCs but did not affect latency. Pirenperone (0.25 mg/kg) prolonged both the latency and duration of the PDCs while pimozide (0.5-2.0 mg/kg) had no effect upon PDCs. This evidence suggests that 5-MeODMT induced changes of PDCs are mediated via 5-HT1 receptors and thus a reliable model to combine with other measures of spinal function is suggested. PMID:3562388

  4. Allergic sensitization modifies the pulmonary expression of 5-hydroxytryptamine receptors in guinea pigs.

    PubMed

    Córdoba-Rodríguez, Guadalupe; Vargas, Mario H; Ruiz, Víctor; Carbajal, Verónica; Campos-Bedolla, Patricia; Mercadillo-Herrera, Paulina; Arreola-Ramírez, José Luis; Segura-Medina, Patricia

    2016-03-01

    There is mounting evidence that 5-hydroxytryptamine (5-HT) plays a role in asthma. However, scarce information exists about the pulmonary expression of 5-HT receptors and its modification after allergic sensitization. In the present work, we explored the expression of 5-HT1A, 5-HT2A, 5-HT3, 5-HT4, 5-ht5a, 5-HT6, and 5-HT7 receptors in lungs from control and sensitized guinea pigs through qPCR and Western blot. In control animals, mRNA from all receptors was detectable in lung homogenates, especially from 5-HT2A and 5-HT4 receptors. Sensitized animals had decreased mRNA expression of 5-HT2A and 5-HT4 receptors and increased that of 5-HT7 receptor. In contrast, they had increased protein expression of 5-HT2A receptor in bronchial epithelium and of 5-HT4 receptor in lung parenchyma. The degree of airway response to the allergic challenge was inversely correlated with mRNA expression of the 5-HT1A receptor. In summary, our results showed that major 5-HT receptor subtypes are constitutively expressed in the guinea pig lung, and that allergic sensitization modifies the expression of 5-HT2A, 5-HT4, and 5-HT7 receptors. PMID:26657047

  5. Inhibitory effect of 5-hydroxytryptamine on penile erectile function in the rat.

    PubMed Central

    Finberg, J. P.; Vardi, Y.

    1990-01-01

    1. An increase in corporal pressure was elicited in pithed rats by stimulation of the sacral part of the spinal cord. This response was inhibited by intravenous injection of 5-hydroxytryptamine (5-HT) (ED50 = 28.5 +/- 2.2 micrograms kg-1). 2. The inhibitory effect of 5-HT was blocked by methysergide and methiothepin (each 1 mg kg-1), but not by ketanserin (0.02 mg kg-1), MDL 72222 (1 mg kg-1) or prazosin (0.1 mg kg-1). 3. An inhibitory effect on the corporal pressure response to spinal stimulation was also produced by 5-carboxyamidotryptamine (ED50 = 5.6 +/- 2.8 micrograms kg-1), but not by m-chlorophenylpiperazine (mCPP), RU 24969, 8-hydroxy-2-[di-n-propyl-amino]-tetralin (8-OH-DPAT) or fenfluramine (doses up to 1-2 mg kg-1). 4. Neither methiothepin (1 mg kg-1) nor clomipramine (1 mg kg-1) had any effect on the frequency-response curve for increase in corporal pressure by spinal stimulation. 5. The results indicate that 5-HT exerts an inhibitory action on penile erection by a peripheral mechanism. This effect may be mediated by vasoconstriction in cavernosal vessels, or inhibition of release of a vasodilator neurotransmitter. From the spectrum of agonist and antagonist responses, the receptor involved may be of the 5-HT1D subtype. PMID:2076486

  6. Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat

    NASA Technical Reports Server (NTRS)

    Kolta, Malak G.; Williams, Byron B.; Soliman, Karam F. A.

    1986-01-01

    The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta-E), and immunoreactive insulin was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) three days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for three days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindolel acetic acid, while it caused significant increase and decrease in brain beta-E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta-E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta-E and insulin regardless of the availability of pancreatic insulin.

  7. Radioimmunoassay of serotonin (5-hydroxytryptamine) in cerebrospinal fluid, plasma, and serum

    SciTech Connect

    Engbaek, F.; Voldby, B

    1982-04-01

    A direct radioimmunoassay is described for serotonin (5-hydroxytryptamine) in cerebrospinal fluid, platelet-poor plasma, and serum. Antisera in rabbits was raised against serotonin diazotized to a conjugate of bovine albumin and D,L-p-aminophenylalanine. Polyethylene glycol, alone or in combination with anti-rabbit immunoglobulins, is used to separate bound and unbound tritiated serotonin. The minimum concentration of serotonin detectable is 2 nmol/L in a 200-..mu..L sample. Within-day precision (CV) is 4.3% between-day precision 7.7%. Analytical recoveries of serotonin are 109% and 101% for cerebrospinal fluid and plasma, respectively. Tryptophan, 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol do not interfere with the assay. However, 5-methoxytryptamine and tryptamine cross react. Of samples of cerebrospinal fluid from patients with disc herniations (n=21) or low-pressure hydrocephalus (n=10), one-third had concentrations of 2-4 nmol/L and two-thirds were below the minimum detectable concentration. The observed range for the concentration of serotonin in plasma of 14 normal subjects was 5-14 nmol/L (mean +/- SD, 9 +/- 3 nmol/L). The observed ranges for serotonin in serum were: for 10 women 520-900 (mean +/- SD: 695 +/- 110) nmol/L and for 10 men 380-680 (520 +/- 94) nmol/L.

  8. Moderate differences in circulating corticosterone alter receptor-mediated regulation of 5-hydroxytryptamine neuronal activity.

    PubMed

    Judge, Sarah J; Ingram, Colin D; Gartside, Sarah E

    2004-12-01

    Circulating glucocorticoid levels vary with stress and psychiatric illness and play a potentially important role in regulating transmitter systems that regulate mood. To determine whether chronic variation in corticosterone levels within the normal diurnal range altered the control of 5-hydroxytryptamine (5-HT) neuronal activity, male rats were adrenalectomized and implanted with either a 2% or 70% corticosterone/cholesterol pellet (100 mg). Two weeks later, the regulation of 5-HT neuronal activity in the dorsal raphe nucleus was studied by in vitro electrophysiology. At this time, serum corticosterone levels approximated the low-point (2%) and mid-point (70%) of the diurnal range. The excitatory response of 5-HT neurones to the alpha1-adrenoceptor agonist phenylephrine (1-11 microM) was significantly greater in the 2% group compared to the 70% group. By contrast, the inhibitory response to 5-HT (10-50 microM) was significantly lower in the 2% group compared to the 70% group. Thus, chronic variation in circulating corticosterone over a narrow part of the normal diurnal range causes a shift in the balance of positive and negative regulation of 5-HT neurones, with increased alpha 1-adrenoceptor-mediated excitation and reduced 5-HT-mediated autoinhibition at lower corticosterone levels. This shift would have a major impact on control of 5-HT neuronal activity. PMID:15582914

  9. Ascorbic acid prevents nonreceptor specific binding of (/sup 3/H)-5-hydroxytryptamine to bovine cerebral cortex membranes

    SciTech Connect

    Hamblin, M.W.; Adriaenssens, P.I.; Ariani, K.; Cawthon, R.M.; Stratford, C.A.; Tan, G.L.; Ciaranello, R.D.

    1987-03-01

    (/sup 3/H)-5-Hydroxytryptamine ((/sup 3/H)-5-HT) decomposes rapidly when exposed to air in solution at physiological pH if antioxidants are not present. The decomposition products appear to bind to two saturable sites on brain membranes (apparent Kd values = 1-2 and 100-1000 nM). This binding mimics ''specific'' ligand/receptor binding in that it is inhibited by 10 microM unlabeled 5-HT. This inhibition is not competitive, but rather is due to the prevention of (/sup 3/H)-5-HT breakdown by excess unlabeled 5-HT. Unlike genuine ligand/receptor binding, the binding of (/sup 3/H)-5-HT breakdown products is essentially irreversible and does not display a tissue distribution consistent with binding to authentic 5-HT receptors. (/sup 3/H)-5-HT decomposition can be eliminated by the inclusion of 0.05 to 5 mM ascorbic acid. At these concentrations ascorbic acid is not deleterious to reversible (/sup 3/H)-5-HT binding. When (/sup 3/H) 5-HT exposure to air occurs in the presence of brain membranes, the apparent antioxidant activity of brain membranes themselves affords protection against (/sup 3/H)-5-HT degradation equal to ascorbic acid. This protection is effective below final (/sup 3/H)-5-HT concentrations of 10 nM. Above 10 nM (/sup 3/H)-5-HT, addition of ascorbic acid or other antioxidants is necessary to avoid the occurrence of additional low affinity (apparent Kd = 15-2000 nM) binding sites that are specific but nonetheless irreversible. When care is taken to limit (/sup 3/H)-5-HT oxidation, the only reversible and saturable specific binding sites observed are of the 5-HT1 high affinity (Kd = 1-2 nM) type. Radioligand oxidation artifacts may be involved in previous reports of low affinity (Kd = 15-250 nM) (/sup 3/H)-5-HT binding sites in brain membrane preparations.

  10. 5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation.

    PubMed

    Darios, Emma S; Barman, Susan M; Orer, Hakan S; Morrison, Shaun F; Davis, Robert P; Seitz, Bridget M; Burnett, Robert; Watts, Stephanie W

    2015-05-01

    Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101±4 to 63±3mm Hg during slow infusion of 5-HT (25μg/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity were unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure. PMID:25732865

  11. Norepinephrine triggers Ca2+-dependent exocytosis of 5-hydroxytryptamine from rat pinealocytes in culture.

    PubMed

    Yamada, Hiroshi; Hayashi, Mitsuko; Uehara, Shunsuke; Kinoshita, Mika; Muroyama, Akiko; Watanabe, Masami; Takei, Koji; Moriyama, Yoshinori

    2002-05-01

    5-hydroxytryptamine (5-HT) is a precursor and a putative modulator for melatonin synthesis in mammalian pinealocytes. 5-HT is present in organelles distinct from l-glutamate-containing synaptic-like microvesicles as well as in the cytoplasm of pinealocytes, and is secreted upon stimulation by norepinephrine (NE) to enhance serotonin N-acetyltransferase activity via the 5-HT2 receptor. However, the mechanism underlying the secretion of 5-HT from pinealocytes is unknown. In this study, we show that NE-evoked release of 5-HT is largely dependent on Ca2+ in rat pinealocytes in culture. Omission of Ca2+ from the medium and incubation of pineal cells with EGTA-tetraacetoxymethyl-ester inhibited by 59 and 97% the NE-evoked 5-HT release, respectively. Phenylephrine also triggered the Ca2+-dependent release of 5-HT, which was blocked by phentolamine, an alpha antagonist, but not by propranolol, a beta antagonist. Botulinum neurotoxin type E cleaved 25 kDa synaptosomal-associated protein and inhibited by 50% of the NE-evoked 5-HT release. Bafilomycin A1, an inhibitor of vacuolar H+-ATPase, and reserpine and tetrabenazine, inhibitors of vesicular monoamine transporter, all decreased the storage of vesicular 5-HT followed by inhibition of the NE-evoked 5-HT release. Agents that trigger L-glutamte exocytosis such as acetylcholine did not trigger any Ca2+-dependent 5-HT release. Vice versa neither NE nor phenylephrine caused synaptic-like microvesicle-mediated l-glutamate exocytosis. These results indicated that upon stimulation of a adrenoceptors pinealocytes secrete 5-HT through a Ca2+-dependent exocytotic mechanism, which is distinct from the exocytosis of synaptic-like microvesicles. PMID:12065661

  12. The role of the 5-hydroxytryptamine pathway in reflux-induced esophageal mucosal injury in rats

    PubMed Central

    2012-01-01

    Background Dysfunction of the 5-hydroxytryptamine (5-HT) signaling pathway can lead to gastrointestinal motility and secretion abnormalities and to visceral hypersensitivity. The aim of this study is to investigate the role of 5-HT in reflux-induced esophageal mucosal injury. Methods Fifty 8-week-old male Sprague-Dawley (SD) rats were randomly divided into a gastroesophageal reflux (GER) model group (30 rats) and a sham surgery control group (20 rats). Four weeks after surgery, the esophageal mucosa was collected for histological evaluation, 5-HT concentrations, and 5-HT selective reuptake transporter (SERT) mRNA and 5-HT4 receptor (5-HT4R) protein expressions. Results Twenty-seven rats in the GER model group survived, and three rats died. Histologically, in the GER model group, 20 rats had reflux esophagitis (RE group), and 7 rats had non-erosive reflux disease (NERD group). The 5-HT levels in the esophageal tissue from the RE group were significantly higher than those from the control and NERD groups. Both the RE and NERD groups showed significant increases in SERT mRNA expression of the esophageal mucosa than that of the controls, and the SERT mRNA level in the RE group was significantly higher than that in the NERD group. The 5-HT4R protein level of the esophageal mucosa in the RE group was significantly lower than that in the controls and the NERD group. Conclusions We conclude that a 5-HT signaling pathway disorder could be a major factor in the pathogenesis of GER and RE. PMID:23092450

  13. A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics.

    PubMed

    Hsu, Eric S

    2010-01-01

    Nausea and vomiting are 2 of the most upsetting adverse reactions of chemotherapy. Current guidelines propose 5-hydroxytryptamine3 (5-HT3) receptor antagonists as a pharmacologic intervention for acute and delayed nausea and vomiting [chemotherapy-induced nausea and vomiting (CINV)] associated with moderately and highly emetogenic chemotherapy. Meanwhile, both postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting are challenging situations after surgeries and procedures. Prophylactic and therapeutic combinations of antiemetics are recommended in patients at high risk of suffering from PONV and postdischarge nausea and vomiting. Granisetron (Kytril) is a selective 5-HT3 receptor antagonist that does not induce or inhibit the hepatic cytochrome P-450 system in vitro. There are also 4 other antagonists of 5-HT3 receptor (dolasetron, ondansetron, palonosetron, and tropisetron) being metabolized via the CYP2D6 and are subject to potential genetic polymorphism. The launch of a new class of antiemetics, the substance P/neurokinin1 receptor antagonists, was attributed to the scientific update on the central generator responsible for emesis and role of substance P. There has been mounting interest in exploring integrative medicine, either acupuncture or acustimulation of P6 (Nei-Kuwan), to complement the western medicine for prevention and management of nausea and vomiting. The potential application of cannabinoids, either alone or in combination with other agents of different mechanism, could contribute further to improve outcome in CINV. Implementation of future treatment guidelines for more effective management of CINV and PONV could certainly improve the efficacy and outcome of cancer and postoperative care. PMID:20844345

  14. Upregulation of 5-Hydroxytryptamine Receptor Signaling in Coronary Arteries after Organ Culture

    PubMed Central

    Rao, Fang; Xue, Yu-Mei; Zhou, Zhi-Ling; Liu, Xiao-Ying; Shan, Zhi-Xin; Li, Xiao-Hong; Lin, Qiu-Xiong; Wu, Shu-Lin; Yu, Xi-Yong

    2014-01-01

    Background 5-Hydroxytryptamine (5-HT) is a powerful constrictor of coronary arteries and is considered to be involved in the pathophysiological mechanisms of coronary-artery spasm. However, the mechanism of enhancement of coronary-artery constriction to 5-HT during the development of coronary artery disease remains to be elucidated. Organ culture of intact blood-vessel segments has been suggested as a model for the phenotypic changes of smooth muscle cells in cardiovascular disease. Methodology/Principal Findings We wished to characterize 5-HT receptor-induced vasoconstriction and quantify expression of 5-HT receptor signaling in cultured rat coronary arteries. Cumulative application of 5-HT produced a concentration-dependent vasoconstriction in fresh and 24 h-cultured rat coronary arteries without endothelia. 5-HT induced greater constriction in cultured coronary arteries than in fresh coronary arteries. U46619- and CaCl2-induced constriction in the two groups was comparable. 5-HT stimulates the 5-HT2A receptor and cascade of phospholipase C to induce coronary vasoconstriction. Calcium influx through L-type calcium channels and non-L-type calcium channels contributed to the coronary-artery constrictions induced by 5-HT. The contractions mediated by non-L-type calcium channels were significantly enhanced in cultured coronary arteries compared with fresh coronary arteries. The vasoconstriction induced by thapsigargin was also augmented in cultured coronary arteries. The decrease in Orai1 expression significantly inhibited 5-HT-evoked entry of Ca2+ in coronary artery cells. Expression of the 5-HT2A receptor, Orai1 and STIM1 were augmented in cultured coronary arteries compared with fresh coronary arteries. Conclusions An increased contraction in response to 5-HT was mediated by the upregulation of 5-HT2A receptors and downstream signaling in cultured coronary arteries. PMID:25202989

  15. 5-Hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation

    PubMed Central

    Darios, Emma S.; Barman, Susan M.; Orer, Hakan S.; Morrison, Shaun F.; Davis, Robert P.; Seitz, Bridget M.; Burnett, Robert; Watts, Stephanie W.

    2015-01-01

    Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101 ± 4 to 63 ± 3 mm Hg during slow infusion of 5-HT (25 μg/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity was unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30 nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure. PMID:25732865

  16. Interferon-γ Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte.

    PubMed

    Zhou, Jia; Ling, Jingjing; Ping, Fengfeng

    2016-01-01

    Interferon-γ (IFN-γ) is an important cytokine which can be secreted by keratinocytes or macrophages induced by UVB irradiation in skin. Mammalian skin cells have the capability to produce and metabolize 5-hydroxytryptamine (5-HT) whose cutaneous effects are mediated by the interactions with 5-HT receptors. Treatment with 5-HT resulted in a dose-dependent increase of tyrosinase (TYR) activity and melanin contents in normal human foreskin-derived epidermal melanocytes (NHEM), while with IFN-γ a decreased effect resulted. These regulatory results were due to changes of the expression levels of microphthalmia-associated transcription factor (MITF) and its downstream TYR, tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase (DCT). We proved here that 5-HTR1A/2A participated in the regulation of melanogenesis. IFN-γ could offset the pro-melanogenesis effect of 5-HT in NHEM and the intensity of this neutralization was unanticipated below the baseline level. IFN-γ neutralized the up-regulation effect of 5-HT on MITF and downstream TYR, TRP-1 and DCT. Though functioning as 5-HT1A/2A receptor during the melanogenesis process, IFN-γ played no role in 5-HT1A/2A receptor expressions. Our results also demonstrated that the inhibition of IFN-γ was reversible after its removal. Confusingly, the effect of cross-talk between 5-HT and IFN-γ on NHEM melanogenesis was irreversible. Whether treated with 5-HT for 5 d or 12 d, the pigmentation level neither recovered after displacing the IFN-γ-containing medium. In addition, IFN-γ was able to inhibit the inductive effect of 5-HT on NHEM migration. Taken together, the suppression of IFN-γ on 5-HT-induced melanogenesis further suggests the negative role of IFN-γ in inflammation-associated pigmentary changes. PMID:27374284

  17. Two cases of mild serotonin toxicity via 5-hydroxytryptamine 1A receptor stimulation

    PubMed Central

    Nakayama, Hiroto; Umeda, Sumiyo; Nibuya, Masashi; Terao, Takeshi; Nisijima, Koichi; Nomura, Soichiro

    2014-01-01

    We propose the possibility of 5-hydroxytryptamine (5-HT)1A receptor involvement in mild serotonin toxicity. A 64-year-old woman who experienced hallucinations was treated with perospirone (8 mg/day). She also complained of depressed mood and was prescribed paroxetine (10 mg/day). She exhibited finger tremors, sweating, coarse shivering, hyperactive knee jerks, vomiting, diarrhea, tachycardia, and psychomotor agitation. After the discontinuation of paroxetine and perospirone, the symptoms disappeared. Another 81-year-old woman, who experienced delusions, was treated with perospirone (8 mg/day). Depressive symptoms appeared and paroxetine (10 mg/day) was added. She exhibited tachycardia, finger tremors, anxiety, agitation, and hyperactive knee jerks. The symptoms disappeared after the cessation of paroxetine and perospirone. Recently, the effectiveness of coadministrating 5-HT1A agonistic psychotropics with selective serotonin reuptake inhibitors (SSRIs) has been reported, and SSRIs with 5-HT1A agonistic activity have been newly approved in the treatment of depression. Perospirone is a serotonin–dopamine antagonist and agonistic on the 5-HT1A receptors. Animal studies have indicated that mild serotonin excess induces low body temperature through 5-HT1A, whereas severe serotonin excess induces high body temperature through 5-HT2A activation. Therefore, it could be hypothesized that mild serotonin excess induces side effects through 5-HT1A, and severe serotonin excess induces lethal side effects with hyperthermia through 5-HT2A. Serotonin toxicity via a low dose of paroxetine that is coadministered with perospirone, which acts agonistically on the 5-HT1A receptor and antagonistically on the 5-HT2A receptor, clearly indicated 5-HT1A receptor involvement in mild serotonin toxicity. Careful measures should be adopted to avoid serotonin toxicity following the combined use of SSRIs and 5-HT1A agonists. PMID:24627634

  18. Increased contractile responses to 5-hydroxytryptamine and Angiotensin II in high fat diet fed rat thoracic aorta

    PubMed Central

    Ghatta, Srinivas; Ramarao, Poduri

    2004-01-01

    Background Feeding normal rats with high dietary levels of saturated fat leads to pathological conditions, which are quite similar to syndrome X in humans. These conditions such as hypertriglyceridemia, hypercholesterolemia, obesity, and hyperglycemia might induce hypertension through various mechanisms. Metabolic syndrome and the resulting NIDDM represent a major clinical challenge because implementation of treatment strategies is difficult. Vascular abnormalities probably contribute to the etiology of many diabetic complications including nephropathy, neuropathy, retinopathy, and cardiomyopathy. It has been shown that in Streptozotocin induced diabetic animals there is an increase in maximal responses to 5-Hydroxytryptamine and Angiotensin II. The purpose of this study was to evaluate High fat diet fed rats for the development of hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia and hyperglycemia and to assess their vascular responses to 5-Hydroxytryptamine and Angiotensin II. Methods Male Sprague Dawley rats were used for this study and were divided into two equal groups. One of the groups was fed with normal pellet diet and they served as the control group, whereas the other group was on a high fat diet for 4 weeks. Body weight, plasma triglycerides, plasma cholesterol, and plasma glucose were measured every week. Intraperitoneal glucose tolerance test was performed after 4 weeks of feeding. At the end of fourth week of high fat diet feeding, thoracic aortae were removed, and cut into helical strips for vascular reactivity studies. Dose-response curves of 5-Hydroxytryptamine and Angiotensin II were obtained. Results There was no significant difference in pD2, with 5-Hydroxytryptamine and Angiotensin II in both groups but Emax was increased. Conclusions These results suggest that hypertension in high fat diet rats is associated with increased in vitro vascular reactivity to 5-HT and Ang II. PMID:15287987

  19. Functional properties of a cloned 5-hydroxytryptamine ionotropic receptor subunit: comparison with native mouse receptors.

    PubMed

    Hussy, N; Lukas, W; Jones, K A

    1994-12-01

    1. A comparative study of the whole-cell and single-channel properties of cloned and native mouse 5-hydroxytryptamine ionotropic receptors (5-HT3) was undertaken using mammalian cell lines expressing the cloned 5-HT3 receptor subunit A (5-HT3R-A), superior cervical ganglia (SCG) neurones and N1E-115 cells. 2. No pharmacological difference was found in the sensitivity to the agonists 5-HT and 2-methyl-5-HT, or to the antagonists d-tubocurare and 3-tropanyl-3,5-dichlorobenzoate (MDL-72222). 3. Current-voltage (I-V) relationships of whole-cell currents showed inward rectification in the three preparations. Rectification was stronger both in cells expressing the 5-HT3R-A subunit and in N1E-115 cells when compared with SCG neurones. 4. No clear openings could be resolved in 5-HT-activated currents in patches excised from cells expressing the 5-HT3R-A subunit or N1E-115 cells. Current fluctuation analysis of whole-cell and excised-patch records revealed a slope conductance of 0.4-0.6 pS in both preparations. Current-voltage relationships of these channels showed strong rectification that fully accounted for the whole-cell voltage dependence. 5. In contrast, single channels of about 10 pS were activated by 5-HT in patches excised from SCG neurones. The weak voltage dependence of their conductance did not account completely for the rectification of whole-cell currents. A lower unitary conductance (3.4 pS) was inferred from whole-cell noise analysis. 6. We conclude that the receptor expressed from the cloned cDNA is indistinguishable from the 5-HT3 receptor of N1E-115 cells, suggesting an identical structure for these two receptors. The higher conductance and different voltage dependence of the 5-HT3 receptor in SCG neurones might indicate the participation of an additional subunit in the structure of native ganglionic 5-HT3 receptors. Homo-oligomeric 5-HT3R-A channels may also be present as suggested by the lower conductance estimated by whole-cell noise analysis. PMID

  20. Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist.

    PubMed

    Zhang, Minli; Zhou, Diansong; Wang, Yi; Maier, Donna L; Widzowski, Daniel V; Sobotka-Briner, Cynthia D; Brockel, Becky J; Potts, William M; Shenvi, Ashok B; Bernstein, Peter R; Pierson, M Edward

    2011-11-01

    The preclinical pharmacology and pharmacokinetic properties of (2R)-6-methoxy-8-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)chromane-2-carboxamide (AZD3783), a potent 5-hydroxytryptamine 1B (5-HT(1B)) receptor antagonist, were characterized as part of translational pharmacokinetic/pharmacodynamic hypothesis testing in human clinical trials. The affinity of AZD3783 to the 5-HT(1B) receptor was measured in vitro by using membrane preparations containing recombinant human or guinea pig 5-HT(1B) receptors and in native guinea pig brain tissue. In vivo antagonist potency of AZD3783 for the 5HT(1B) receptor was investigated by measuring the blockade of 5-HT(1B) agonist-induced guinea pig hypothermia. The anxiolytic-like potency was assessed using the suppression of separation-induced vocalization in guinea pig pups. The affinity of AZD3783 for human and guinea pig 5-HT(1B) receptor (K(i), 12.5 and 11.1 nM, respectively) was similar to unbound plasma EC(50) values for guinea pig receptor occupancy (11 nM) and reduction of agonist-induced hypothermia (18 nM) in guinea pig. Active doses of AZD3783 in the hypothermia assay were similar to doses that reduced separation-induced vocalization in guinea pig pups. AZD3783 demonstrated favorable pharmacokinetic properties. The predicted pharmacokinetic parameters (total plasma clearance, 6.5 ml/min/kg; steady-state volume of distribution, 6.4 l/kg) were within 2-fold of the values observed in healthy male volunteers after a single 20-mg oral dose. This investigation presents a direct link between AZD3783 in vitro affinity and in vivo receptor occupancy to preclinical disease model efficacy. Together with predicted human pharmacokinetic properties, we have provided a model for the quantitative translational pharmacology of AZD3783 that increases confidence in the optimal human receptor occupancy required for antidepressant and anxiolytic effects in patients. PMID:21825000

  1. Modulation of 5-hydroxytryptamine efflux from rat cortical synaptosomes by opioids and nociceptin

    PubMed Central

    Sbrenna, S; Marti, M; Morari, M; Calo', G; Guerrini, R; Beani, L; Bianchi, C

    2000-01-01

    The modulation of [3H]-5-hydroxytryptamine ([3H]-5-HT) efflux from superfused rat cortical synaptosomes by delta, kappa, mu and ORL1 opioid receptor agonists and antagonists was studied. Spontaneous [3H]-5-HT efflux was reduced (20% inhibition) by either 0.5 μM tetrodotoxin or Ca2+-omission. Ten mM K+-evoked [3H]-5-HT overflow was largely Ca2+-dependent (90%) and tetrodotoxin-sensitive (50%). The delta receptor agonist, deltorphin-I, failed to modulate the K+-evoked neurotransmitter efflux up to 0.3 μM. The kappa and the mu receptor agonists, U-50,488 and endomorphin-1, inhibited K+-evoked [3H]-5-HT overflow (EC50=112 and 7 nM, respectively; Emax=28 and 29% inhibition, respectively) in a norBinaltorphimine- (0.3 μM) and naloxone- (1 μM) sensitive manner, respectively. None of these agonists significantly affected spontaneous [3H]-5-HT efflux. The ORL1 receptor agonist nociceptin inhibited both spontaneous (EC50=67 nM) and K+-evoked (EC50=13 nM; Emax=52% inhibition) [3H]-5-HT efflux. The effect of NC was insensitive to naloxone (up to 10 μM), but was antagonized by [Nphe1]nociceptin(1-13)NH2 (a novel selective ORL1 receptor antagonist; pA2=6.7) and by naloxone benzoylhydrazone (pA2=6.3). The ORL1 ligand [Phe1ψ(CH2-NH)Gly2]nociceptin(1-13)NH2 also inhibited K+ stimulated [3H]-5-HT overflow (EC50=64 nM; Emax=31% inhibition), but its effect was partially antagonized by 10 μM naloxone. It is concluded that the ORL1 receptor is the most important presynaptic modulator of neocortical 5-HT release within the opioid receptor family. This suggests that the ORL1/nociceptin system may have a powerful role in the control of cerebral 5-HT-mediated biological functions. PMID:10807682

  2. Effects of metformin on intestinal 5-hydroxytryptamine (5-HT) release and on 5-HT3 receptors.

    PubMed

    Cubeddu, L X; Bönisch, H; Göthert, M; Molderings, G; Racké, K; Ramadori, G; Miller, K J; Schwörer, H

    2000-01-01

    Nearly 30% of patients treated with metformin experience gastrointestinal side effects. Since release of 5-hydroxytryptamine (5-HT) from the intestine is associated with nausea, vomiting, and diarrhea, we examined whether metformin induces 5-HT release from the intestinal mucosa. In 40% of tissue biopsy specimens of human duodenal mucosa, metformin (1, 10, and 30 microM) caused an increase in 5-HT outflow by 35, 70, and 98%, respectively. Peak increases in 5-HT outflow were observed after 10-15 min exposure to metformin, returning to baseline levels after 25 min. Tetrodotoxin (1 microM) reduced by about 50% the metformin-evoked increase in 5-HT outflow (P<0.05). Metformin-evoked release was not affected by scopolamine + hexamethonium, propranolol, the 5-HT3 receptor antagonist dolasetron, naloxone, or the NK1 receptor antagonist L703606. In the presence of tetrodotoxin (1 microM), somatostatin (1 microM) further reduced metformin-induced 5-HT release by 15-20%. In view of the 5-HT releasing effects of selective 5-HT3 receptor agonists to which metformin (N-N-dimethylbiguanide) is structurally related, we investigated whether metformin directly interacts with 5-HT3 receptors. Receptor binding (inhibition of [3H]-GR65630 binding) and agonist effects (stimulation of [14C]-guanidinium influx) at 5-HT3 receptors were studied in murine neuroblastoma N1E-115 cells, which express functional 5-HT3 receptors. Metformin up to 0.3 mM failed to inhibit [3H]-GR65630 binding and to modify displacement of [3H]-GR65630 binding induced by 5-HT. 5-HT (3 microM) stimulated the influx of [14C]-guanidinium in intact N1E-115 cells. Metformin up to 1 mM failed to modify basal influx, 5-HT-induced influx, and 5-HT+ substance P-induced influx of [14C]-guanidinium. Our results indicate that metformin induces 5-HT3 receptor-independent release of 5-HT from human duodenal mucosa via neuronal and non-neuronal mechanisms. Part of the gastrointestinal side effects observed during treatment with

  3. 5-Hydroxytryptamine promotes hepatocellular carcinoma proliferation by influencing β-catenin.

    PubMed

    Fatima, Sarwat; Shi, Xiaoke; Lin, Zesi; Chen, Guo-Qing; Pan, Xiao-Hua; Wu, Justin Che-Yuen; Ho, John W; Lee, Nikki P; Gao, Hengjun; Zhang, Ge; Lu, Aiping; Bian, Zhao Xiang

    2016-02-01

    5-Hydroxytryptamine (5-HT), a neurotransmitter and vasoactive factor, has been reported to promote proliferation of serum-deprived hepatocellular carcinoma (HCC) cells but the detailed intracellular mechanism is unknown. As Wnt/β-catenin signalling is highly dysregulated in a majority of HCC, this study explored the regulation of Wnt/β-catenin signalling by 5-HT. The expression of various 5-HT receptors was studied by quantitative real-time polymerase chain reaction (qPCR) in HCC cell lines as well as in 33 pairs of HCC tumours and corresponding adjacent non-tumour tissues. Receptors 5-HT1D (21/33, 63.6%), 5-HT2B (12/33, 36.4%) and 5-HT7 (15/33, 45.4%) were overexpressed whereas receptors 5-HT2A (17/33, 51.5%) and 5-HT5 (30/33, 90.1%) were reduced in HCC tumour tissues. In vitro data suggests 5-HT increased total β-catenin, active β-catenin and decreased phosphorylated β-catenin protein levels in serum deprived HuH-7 and HepG2 cells compared to control cells under serum free medium without 5-HT. Activation of Wnt/β-catenin signalling was evidenced by increased expression of β-catenin downstream target genes, Axin2, cyclin D1, dickoppf-1 (DKK1) and glutamine synthetase (GS) by qPCR in serum-deprived HCC cell lines treated with 5-HT. Additionally, biochemical analysis revealed 5-HT disrupted Axin1/β-catenin interaction, a critical step in β-catenin phosphorylation. Increased Wnt/β-catenin activity was attenuated by antagonist of receptor 5-HT7 (SB-258719) in HCC cell lines and patient-derived primary tumour tissues in the presence of 5-HT. SB-258719 also reduced tumour growth in vivo. This study provides evidence of Wnt/β-catenin signalling activation by 5-HT and may represent a potential therapeutic target for hepatocarcinogenesis. PMID:26474915

  4. Characterization of the 5-hydroxytryptamine receptors mediating contraction in the pig isolated intravesical ureter

    PubMed Central

    Hernández, Medardo; Barahona, María Victoria; Simonsen, Ulf; Recio, Paz; Rivera, Luis; Martínez, Ana Cristina; García-Sacristán, Albino; Orensanz, Luis M; Prieto, Dolores

    2003-01-01

    This study was designed to investigate the effect of 5-hydroxytryptamine (5-HT) and to characterize the 5-HT receptors involved in 5-HT responses in the pig intravesical ureter. 5-HT (0.01–10 μM) concentration-dependently increased the tone of intravesical ureteral strips, whereas the increases in phasic contractions were concentration-independent. The 5-HT2 receptor agonist α-methyl 5-HT, mimicked the effect on tone whereas weak or no response was obtained with 5-CT, 8-OH-DPAT, m-chlorophenylbiguanide and RS 67333, 5-HT1, 5-HT1A, 5-HT3 and 5-HT4 receptor agonists, respectively. 5-HT did not induce relaxation of U46619-contracted ureteral preparations. Pargyline (100 μM), a monoaminooxidase A/B activity inhibitor, produced leftward displacements of the concentration-response curves for 5-HT. 5-HT-induced tone was reduced by the 5-HT2 and 5-HT2A receptor antagonists ritanserine (0.1 μM) and spiperone (0.2 μM), respectively. However, 5-HT contraction was not antagonized by cyanopindolol (2 μM), SDZ–SER 082 (1 μM), Y-25130 (1 μM) and GR 113808 (0.1 μM), which are respectively, 5-HT1A/1B, 5-HT2B/2C, 5-HT3, and 5-HT4 selective receptor antagonists. Removal of the urothelium did not modify 5-HT-induced contractions. Blockade of neuronal voltage-activated sodium channels, α-adrenergic receptors and adrenergic neurotransmission with tetrodotoxin (1 μM), phentolamine (0.3 μM) and guanethidine (10 μM), respectively, reduced the contractions to 5-HT. However, physostigmine (1 μM), atropine (0.1 μM) and suramin (30 μM), inhibitors of cholinesterase activity, muscarinic- and purinergic P2-receptors, respectively, failed to modify the contractions to 5-HT. These results suggest that 5-HT increases the tone of the pig intravesical ureter through 5-HT2A receptors located at the smooth muscle. Part of the 5-HT contraction is indirectly mediated via noradrenaline release from sympathetic nerves. PMID:12522083

  5. Arachidonate metabolism, 5-hydroxytryptamine release and aggregation in human platelets activated by palmitaldehyde acetal phosphatidic acid.

    PubMed Central

    Brammer, J. P.; Maguire, M. H.

    1984-01-01

    Palmitaldehyde acetal phosphatidic acid ( PGAP ) caused dose-dependent aggregation of human platelets resuspended in modified Tyrode medium, with a threshold concentration of 0.5-1 microM and an EC50 of 4 microM. Concentrations of PGAP which elicited biphasic irreversible aggregation concomitantly induced formation of 1.02 +/- 0.029 nmol (mean +/- s.e. mean) of malondialdehyde (MDA) per 10(9) platelets and caused release of 58 +/- 2.8% of platelet [14C]-5-hydroxytryptamine ([14C]-5-HT) from prelabelled platelets; no MDA formation or [14C]-5-HT release occurred at lower doses of PGAP which elicited only monophasic reversible aggregation. Adenosine 5'-pyrophosphate (ADP)-induced platelet activation resulted in formation of 0.344 +/- 0.004 nmol of MDA per 10(9) platelets in association with irreversible aggregation and 49.1 +/- 1% release of [14C]-5-HT. Mepacrine, a phospholipase A2 inhibitor, at 2.5 microM reduced PGAP -induced MDA formation and [14C]-5-HT release by the resuspended platelets without affecting irreversible aggregation; higher concentrations of mepacrine abolished all three responses. Chlorpromazine, a calmodulin antagonist, similarly inhibited PGAP -induced MDA formation and irreversible aggregation, and at 100 microM abolished monophasic aggregation. The cyclo-oxygenase inhibitor indomethacin caused a concentration-dependent reduction of PGAP -induced MDA formation by resuspended human platelets without significantly inhibiting [14C]-5-HT release or irreversible aggregation; concentrations (greater than or equal to 1.75 microM) which inhibited MDA formation by more than 94% abolished [14C]-5-HT release, and converted second phase irreversible aggregation to an extensive reversible response. 2-Methylthioadenosine 5'-phosphate (2 methylthio-AMP), an ADP antagonist, inhibited PGAP -induced MDA formation, [14C]-5-HT release and second phase aggregation in the human platelet suspensions in a parallel, concentration-dependent manner; at 9.4 microM 2

  6. Regulation of rat cortical 5-hydroxytryptamine2A-receptor mediated electrophysiological responses by repeated daily treatment with electroconvulsive shock or imipramine

    PubMed Central

    Marek, Gerard J.

    2008-01-01

    Down-regulation of 5-hydroxytryptamine2A (5-HT2A) receptors has been a consistent effect induced by most antidepressant drugs. In contrast, electroconvulsive shock (ECS) up-regulates the number of 5-HT2A receptor binding sites. However, the effects of antidepressants on 5-HT2A receptor-mediated responses on identified cells of the cerebral cortex has not been examined. The purpose of the present study was to compare the effects of the tricyclic antidepressant imipramine and ECS on 5-HT2A receptor-mediated electrophysiological responses involving glutamatergic and GABAergic neurotransmission in the rat medial prefrontal cortex (mPFC) and piriform cortex, respectively. The electrophysiological effects of activating 5-HT2A receptors was consistent with 5-HT2A receptor binding regulation for imipramine and ECS except for the mPFC where chronic ECS decreased the potency of 5-HT at a 5-HT2A receptor-mediated response. These findings are consistent with the general hypothesis that chronic antidepressant treatments shift the balance of serotonergic neurotransmission towards inhibitory effects in the cortex. PMID:18294819

  7. Molecular modelling of human 5-hydroxytryptamine receptor (5-HT2A) and virtual screening studies towards the identification of agonist and antagonist molecules.

    PubMed

    Gandhimathi, A; Sowdhamini, R

    2016-05-01

    The serotonin receptors, also known as 5-hydroxytryptamine (5-HT) receptors, are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels found in the central and peripheral nervous systems. GPCRs have a characteristic feature of activating different signalling pathways upon ligand binding and these ligands display several efficacy levels to differentially activate the receptor. GPCRs are primary drug targets due to their central role in several signal transduction pathways. Drug design for GPCRs is also most challenging due to their inherent promiscuity in ligand recognition, which gives rise to several side effects of existing drugs. Here, we have performed the ligand interaction study using the two prominent states of GPCR, namely the active and inactive state of the 5-HT2A receptor. Active state of 5-HT2A receptor model enhances the understanding of conformational difference which influences the ligand-binding site. A 5-HT2A receptor active state model was constructed by homology modelling using active state β2-adrenergic receptor (β2-AR). In addition, virtual screening and docking studies with both active and inactive state models reveal potential small molecule hits which could be considered as agonist-like and antagonist-like molecules. The results from the all-atom molecular dynamics simulations further confirmed that agonists and antagonists interact in different modes with the receptor. PMID:26327576

  8. 5-Hydroxytryptamine 4(a) receptor expressed in Sf9 cells is palmitoylated in an agonist-dependent manner.

    PubMed Central

    Ponimaskin, E G; Schmidt, M F; Heine, M; Bickmeyer, U; Richter, D W

    2001-01-01

    The mouse 5-hydroxytryptamine 4(a) receptor [5-HT(4(a))] was expressed with a baculovirus system in insect cells and analysed for acylation. [(3)H]Palmitic acid was effectively incorporated into 5-HT(4(a)) and label was sensitive to the treatment with reducing agents indicating a thioester-type bond. Analysis of protein-bound fatty acids revealed that 5-HT(4(a)) contains predominantly palmitic acid. Treatment of infected Sf9 (Spodoptera frugiperda) cells with BIMU8 [(endo-N-8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dehydro-2-oxo-3-(prop-2-yl)-1H-benzimid-azole-1-carboxamide], a 5-HT(4) receptor-selective agonist, generated a dose-dependent increase in [(3)H]palmitate incorporation into 5-HT(4(a)) with an EC(50) of approx. 10 nM. The change in receptor labelling after stimulation with agonist was receptor-specific and did not result from general metabolic effects. We also used both pulse labelling and pulse-chase labelling to address the dynamics of 5-HT(4(a)) palmitoylation. Incorporation studies revealed that the rate of palmitate incorporation was increased approx. 3-fold after stimulation with agonist. Results of pulse-chase experiments show that activation with BIMU8 promoted the release of radiolabel from 5-HT(4(a)), thereby reducing the levels of receptor-bound palmitate to approximately one-half. Taken together, our results demonstrate that palmitoylation of 5-HT(4(a)) is a reversible process and that stimulation of 5-HT(4(a)) with agonist increases the turnover rate for receptor-bound palmitate. This provides evidence for a regulated cycling of receptor-bound palmitate and suggests a functional role for palmitoylation/depalmitoylation in 5-hydroxytryptamine-mediated signalling. PMID:11171060

  9. Measuring the serotonin uptake site using (/sup 3/H)paroxetine--a new serotonin uptake inhibitor

    SciTech Connect

    Gleiter, C.H.; Nutt, D.J.

    1988-01-01

    Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand.

  10. Differentiation of 5-hydroxytryptamine2 receptor subtypes using sup 125 I-R-(-)2,5-dimethoxy-4-iodo-phenylisopropylamine and sup 3 H-ketanserin

    SciTech Connect

    McKenna, D.J.; Peroutka, S.J. )

    1989-10-01

    The radioligand binding characteristics of 125I-R-(-)4-iodo-2,5-dimethoxyphenylisopropylamine (125I-R-(-)DOI) and 3H-ketanserin were compared in rat and bovine cortical membranes. In rat cortex, 125I-R-(-)DOI labels a relatively low density of binding sites (Bmax = 2.5 +/- 0.2 pmol/gm tissue) with high affinity (KD = 0.63 +/- 0.09 nM). In bovine cortex, specific binding of 125I-R-(-)DOI represents less than 20% of total binding at radioligand concentrations above 0.6 nM, and, therefore, the data cannot be analyzed adequately by Scatchard transformation. By contrast, 3H-ketanserin displays saturable, specific high-affinity binding in both rat cortex (KD = 1.0 +/- 0.1 nM; Bmax = 11 +/- 0.4 pmol/gm tissue) and bovine cortex (KD = 1.2 +/- 0.2 nM; Bmax = 5.3 +/- 0.4 pmol/gm tissue). Ki values for 30 drugs were determined for 125I-R-(-)DOI-labeled sites in rat cortex and 3H-ketanserin-labeled sites in bovine cortex. 5-Hydroxytryptamine (5-HT) displays 250-fold higher selectivity for the 125I-R-(-)DOI-labeled sites (Ki = 3.0 +/- 0.7 nM) than for the 3H-ketanserin-labeled sites (Ki = 750 +/- 50 nM). Structural congeners of R-(-)DOI display 80- to 160-fold higher affinity for the 125I-R-(-)DOI binding site than for the 3H-ketanserin-labeled binding site. d-LSD and putative 5-HT2 antagonists are approximately equipotent at both sites. Significant correlations were found between drug affinities for 125I-R-(-)DOI-labeled sites in rat cortex and putative 5-HT2A sites labeled previously by 77Br-R-(-)DOB (r = 0.93, p less than 0.01), putative 5-HT2B sites labeled by 3H-ketanserin in bovine cortex (r = 0.63, p less than 0.01), and 5-HT1C binding sites that have been characterized by other investigators (r = 0.78, p less than 0.01). No significant correlations were found between drug affinities for 125I-R-(-)DOI-labeled sites in rat cortex and 5-HT1A, 5-HT1B, 5-HT1D, or 5-HT3 sites, as determined by previous investigators.

  11. Antagonism of 5-hydroxytryptamine2A Receptor Results in Decreased Contractile Response of Bovine Lateral Saphenous Vein to Tall Fescue Alkaloids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pharmacologic profiling of 5-hydroxytryptamine (5HT) receptors of bovine lateral saphenous vein has shown that cattle grazing endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have altered responses to ergovaline (ERV), 5HT, 5HT2A and 5HT7 agonists. To determine if 5HT...

  12. Cinitapride protects against ethanol-induced gastric mucosal injury in rats: role of 5-hydroxytryptamine, prostaglandins and sulfhydryl compounds.

    PubMed

    Alarcón-de-la-Lastra Romero, C; López, A; Martín, M J; la Casa, C; Motilva, V

    1997-04-01

    This study was designed to determine the gastroprotective properties of cinitapride (CNT), a novel prokinetic benzamide derivative agonist of 5-HT4 and 5-HT1 receptors and 5-HT2 antagonist, on mucosal injury produced by 50% (v/v) ethanol. Results were compared with those for 5-hydroxytryptamine (5-HT: 10 mg kg-1). The possible involvements of gastric mucus secretion, endogenous prostaglandins (PGs) and sulfhydryl compounds (SH) in the protection mediated by CNT were also examined. Intraperitoneal administration of CNT (0.50 and 1 mg kg-1), 30 min before ethanol, significantly prevented gastric ulceration and increased the hexosamine content of gastric mucus. CNT (1 mg kg-1) also produced a significant increase in gastric mucosal levels of PGE2, but did not induce any significant changes in SH values. On the contrary, pretreatment with 5-HT worsened ethanol-induced erosions, however, did not affect gastric mucus secretion, glycoprotein content or PGE2 levels, although the non-protein SH fraction was significantly decreased. The present results demonstrate that the gastroprotective effects of CNT could be partly explained by a complex PG dependent mechanism. We suggest that 5-HT dependent mechanisms through 5-HT2 receptor blockade and 5-HT1 receptor activation could be also involved. PMID:9211565

  13. Water-soluble jack-knife prawn extract inhibits 5-hydroxytryptamine-induced vasoconstriction and platelet aggregation in humans.

    PubMed

    Gamoh, Shuji; Kanai, Tasuku; Tanaka-Totoribe, Naoko; Ohkura, Masamichi; Kuwabara, Masachika; Nakamura, Eisaku; Yokota, Atsuko; Yamasaki, Tetsuo; Watanabe, Akiko; Hayashi, Masahiro; Fujimoto, Shouichi; Yamamoto, Ryuichi

    2015-02-01

    Coronary artery spasm plays an important role in the pathogenesis of various ischemic heart diseases or serious arrhythmia. The aim of this study is to look for functional foods which have physiologically active substances preventing 5-hydroxytryptamine (5-HT)-related vasospastic diseases including peri- and postoperative ischemic complications of coronary artery bypass grafting (CABG) from ocean resources in Japanese coastal waters. First, we evaluated the effect of water-soluble ocean resource extracts on the response to 5-HT in HEK293 cells which have forcibly expressed cyan fluorescent protein-fused 5-HT2A receptors (5-HT2A-CFP). Among 5 different water-soluble extracts of ocean resources, the crude water-soluble jack-knife prawn extract (WJPE) significantly reduced maximal Ca(2+) influx induced by 0.1 μM 5-HT in a concentration-dependent manner. The Crude WJPE significantly inhibited, in a concentration-dependent manner, 5-HT-induced constriction of human saphenous vein. 5-HT released from activated platelets plays a crucial roles in the constriction of coronary artery. Next the WJPE was purified for applying the experiment of 5-HT-induced human platelet aggregation. The purified WJPE significantly inhibited 5-HT-induced human platelet aggregation also in a concentration-dependent manner. Based on our findings, jack-knife prawn could be one of a functional food with health-promoting benefits for most people with vasospastic diseases including patients who have gone CABG. PMID:25464143

  14. Alterations of Ca(v)1.2 and 5-hydroxytryptamine in rat hearts after positional asphyxia.

    PubMed

    Li, X-F; Huang, Q-Y

    2015-01-01

    We investigated alterations of cardiac Ca(v)1.2 and 5-hydroxytryptamine (5-HT) associated with positional asphyxia. Male rats were divided into five groups: a control group with no restraint, group 1 restrained for 1 h, group 2 restrained for 2 h, group 3 restrained for 4 h, and group 4 restrained for 8 h. The rats that were restrained for 8 h ultimately suffered fatal asphyxia. After the restraint periods, the rats were sacrificed and immunohistochemistry was performed to evaluate the expressions of Ca(v)1.2 and 5-HT in the heart. Sections were analyzed by digital image analysis. Cardiac expression of Ca(v)1.2 and 5-HT proteins were significantly decreased by positional asphyxia in the rat, shown by integrated optical density (IOD) compared to controls. Our findings indicate that Ca(v)1.2 and 5-HT alterations could cause abnormal cardiac function, and the proteins investigated here may be useful for investigating the mechanisms underlying positional asphyxia. PMID:26471941

  15. 5-Hydroxytryptamine 1A and 2B serotonin receptors in neurite outgrowth: involvement of early growth response protein 1.

    PubMed

    Anelli, Tonino; Cardarelli, Silvia; Ori, Michela; Nardi, Irma; Biagioni, Stefano; Poiana, Giancarlo

    2013-01-01

    Neurotransmitters play important roles in neurogenesis; in particular, acetylcholine and serotonin may regulate neurite elongation. Acetylcholine may also activate transcription factors such as early growth response protein 1 (EGR-1), which plays a role in neurite extension. N18TG2 neuroblastoma cells (which do not produce neurotransmitters and constitutively express muscarinic acetylcholine receptors) were transfected with constructs containing the cDNA for choline acetyltransferase, 5-hydroxytryptamine 1A (5-HT1A) and 5-HT2B serotonin receptors to study acetylcholine and serotonin interplay in neurite outgrowth. 5-HT1A receptor stimulation causes a decrease in EGR-1 levels and inhibition of neurite outgrowth; 5-HT2B stimulation, however, has no effect. Muscarinic cholinergic stimulation, on the other end, increases EGR-1 levels and fiber outgrowth. Inhibition of EGR-1 binding reduces fiber outgrowth activity. When both cholinergic and 5-HT1A receptors are stimulated, fiber outgrowth is restored; therefore, acetylcholine counterbalances the inhibitory effect of serotonin on neurite outgrowth. These results suggest that EGR-1 plays a role in the interplay of acetylcholine and serotonin in the regulation of neurite extension during development. PMID:24158140

  16. Effects of morphine, physostigmine and raphe nuclei stimulation on 5-hydroxytryptamine release from the cerebral cortex of the cat.

    PubMed Central

    Aiello-Malmberg, P; Bartolini, A; Bartolini, R; Galli, A

    1979-01-01

    1. The release of 5-hydroxytryptamine (5-HT) from the cerebral cortex and caudate nucleus of brainstem-transected cats and from the cerebral cortex of rats anaesthetized with urethane was determined by radioenzymatic and biological assay. 2. The stimulation of nucleus linearis intermedius of raphe doubles the basal 5-HT release in the caudate nucleus and increases it 3 fold in the cerebral cortex. The effects of the electrical stimulation of the raphe are potentiated by chlorimipramine. 3. Brain 5-HT release is greatly increased by morphine hydrochloride (6 mg/kg i.v.) and by physostigmine (100 microgram/kg i.v.), but not by DL-DOPA (50 mg/kg i.v.). 4. It is suggested that the 5-HT releasing action of physostigmine can contribute to some of its pharmacological effects such as the analgesic effect so far attributed exclusively to its indirect cholinomimetic activity. 5. The 5-HT releasing action of physostigmine seems unrelated to its anticholinesterase activity. PMID:435680

  17. Quercetin inhibits the 5-hydroxytryptamine type 3 receptor-mediated ion current by interacting with pre-transmembrane domain I.

    PubMed

    Lee, Byung-Hwan; Jeong, Sang-Min; Jung, Sang-Min; Lee, Jun-Ho; Kim, Jong-Hoon; Yoon, In-Soo; Lee, Joon-Hee; Choi, Sun-Hye; Lee, Sang-Mok; Chang, Choon-Gon; Kim, Hyung-Chun; Han, YeSun; Paik, Hyun-Dong; Kim, Yangmee; Nah, Seung-Yeol

    2005-08-31

    The flavonoid, quercetin, is a low molecular weight substance found in apple, tomato and other fruit. Besides its antioxidative effect, quercetin, like other flavonoids, has a wide range of neuropharmacological actions including analgesia, and motility, sleep, anticonvulsant, sedative and anxiolytic effects. In the present study, we investigated its effect on mouse 5-hydroxytryptamine type 3 (5-HT3A) receptor channel activity, which is involved in pain transmission, analgesia, vomiting, and mood disorders. The 5-HT3A receptor was expressed in Xenopus oocytes, and the current was measured with the two-electrode voltage clamp technique. In oocytes injected with 5-HT3A receptor cRNA, quercetin inhibited the 5-HT-induced inward peak current (I(5-HT)) with an IC50 of 64.7 +/- 2.2 microM. Inhibition was competitive and voltage-independent. Point mutations of pre-transmembrane domain 1 (pre-TM1) such as R222T and R222A, but not R222D, R222E and R222K, abolished inhibition, indicating that quercetin interacts with the pre-TM1 of the 5-HT3A receptor. PMID:16258243

  18. 5-Hydroxytryptamine-induced bladder hyperactivity via the 5-HT2A receptor in partial bladder outlet obstruction in rats.

    PubMed

    Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

    2013-04-01

    We investigated the effects of partial bladder outlet obstruction (BOO) on the function and gene expression of 5-hydroxytryptamine (5-HT) receptor subtypes in rat bladder. Isometric contractions of the isolated bladders from sham-operated control and BOO rats were examined. The contractile responses to 5-HT were significantly increased in BOO rat bladder strips, while the responses to KCl, carbachol, or phenylephrine were not different from the control. The 5-HT-induced hypercontraction in BOO rat bladder strips was inhibited by ketanserin, a 5-HT(2A) receptor antagonist. The contractile responses to 5-HT in bladder strips were not affected by urothelium removal from the intact bladder. The gene expression of 5-HT receptor subtypes in the bladders was analyzed by RT-PCR. The mRNA expression of the 5-HT(2A), 5-HT(2B), 5-HT(2C), 5-HT(4), and 5-HT(7) receptors was detected in both the control and BOO rat bladders. Quantitative RT-PCR analysis showed there was a significant increase of 5-HT(2A) receptor mRNA in the BOO rat bladder compared with the control bladder. On the other hand, the gene expression of the 5-HT(4) receptor was not changed in the BOO rat bladder. These results suggest that the increased contractile responses to 5-HT in BOO rat bladder may be partly caused by 5-HT(2A) receptor upregulation in the detrusor smooth muscles. PMID:23344575

  19. Toward Selective Drug Development for the Human 5-Hydroxytryptamine 1E Receptor: A Comparison of 5-Hydroxytryptamine 1E and 1F Receptor Structure-Affinity RelationshipsS⃞

    PubMed Central

    Klein, Michael T.; Dukat, Małgorzata; Glennon, Richard A.

    2011-01-01

    The 5-hydroxytryptamine (5-HT) 1E receptor is highly expressed in the human frontal cortex and hippocampus, and this distribution suggests the function of 5-HT1E receptors might be linked to memory. To test this hypothesis, behavioral experiments are needed. Because rats and mice lack a 5-HT1E receptor gene, knockout strategies cannot be used to elucidate this receptor's functions. Thus, selective pharmacological tools must be developed. The tryptamine-related agonist BRL54443 [5-hydroxy-3-(1-methylpiperidin-4-yl)-1H-indole] is one of the few agents that binds 5-HT1E receptors with high affinity and some selectively; unfortunately, it binds equally well to 5-HT1F receptors (Ki ≈ 1 nM). The differences between tryptamine binding requirements of these two receptor populations have never been extensively explored; this must be done to guide the design of analogs with greater selectivity for 5-HT1E receptors versus 5-HT1F receptors. Previously, we determined the receptor binding affinities of a large series of tryptamine analogs at the 5-HT1E receptor; we now examine the affinities of this same series of compounds at 5-HT1F receptors. The affinities of these compounds at 5-HT1E and 5-HT1F receptors were found to be highly correlated (r = 0.81). All high-affinity compounds were full agonists at both receptor populations. We identified 5-N-butyryloxy-N,N-dimethyltryptamine as a novel 5-HT1F receptor agonist with >60-fold selectivity versus 5-HT1E receptors. There is significant overlap between 5-HT1E and 5-HT1F receptor orthosteric binding properties; thus, identification of 5-HT1E-selective orthosteric ligands will be difficult. The insights generated from this study will inform future drug development and molecular modeling studies for both 5-HT1E and 5-HT1F receptors. PMID:21422162

  20. Increased extracellular dopamine and 5-hydroxytryptamine levels contribute to enhanced subthalamic nucleus neural activity during exhausting exercise.

    PubMed

    Hu, Y; Liu, X; Qiao, D

    2015-09-01

    The purpose of the study was to explore the mechanism underlying the enhanced subthalamic nucleus (STN) neural activity during exhausting exercise from the perspective of monoamine neurotransmitters and changes of their corresponding receptors. Rats were randomly divided into microdialysis and immunohistochemistry study groups. For microdialysis study, extracellular fluid of the STN was continuously collected with a microdialysis probe before, during and 90 min after one bout of exhausting exercise. Dopamine (DA) and 5-hydroxytryptamine (5-HT) levels were subsequently detected with high-performance liquid chromatography (HPLC). For immunohistochemistry study, the expression of DRD2 and HT2C receptors in the STN, before, immediately after and 90 min after exhaustion was detected through immunohistochemistry technique. Microdialysis study results showed that the extracellular DA and 5-HT neurotransmitters increased significantly throughout the procedure of exhausting exercise and the recovery period (P<0.05 or P<0.01). Immunohistochemistry study results showed that the expression levels of DRD2 and HT2C in the rat STN immediately after exhausting exercise and at the time point of 90 min after exhaustion were both higher than those of the rest condition, but the difference was not significant (P>0.05). Our results suggest that the increased extracellular DA and 5-HT in the STN might be one important factor leading to the enhanced STN neural activity and the development of fatigue during exhausting exercise. This study may essentially offer useful evidence for better understanding of the mechanism of the central type of exercise-induced fatigue. PMID:26424920

  1. Tong Xie Yao Fang relieves irritable bowel syndrome in rats via mechanisms involving regulation of 5-hydroxytryptamine and substance P

    PubMed Central

    Yin, Yue; Zhong, Lei; Wang, Jian-Wei; Zhao, Xue-Ying; Zhao, Wen-Jing; Kuang, Hai-Xue

    2015-01-01

    AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang (TXYF) improves dysfunction in an irritable bowel syndrome (IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats (1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine (5-HT) and substance P (SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity. RESULTS: Defecation frequency was 1.8 ± 1.03 in normal rats and 4.5 ± 1.58 in IBS model rats (P < 0.001). However, the defecation frequency was significantly decreased (3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time (in seconds) of colon transit function was significantly increased (256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS. PMID:25914462

  2. Nocistatin inhibits 5-hydroxytryptamine release in the mouse neocortex via presynaptic Gi/o protein linked pathways

    PubMed Central

    Fantin, M; Fischetti, C; Trapella, C; Morari, M

    2007-01-01

    Background and purpose: Nocistatin (NST) is a neuropeptide generated from cleavage of the nociceptin/orphanin FQ (N/OFQ) precursor. Evidence has been presented that NST acts as a functional antagonist of N/OFQ, although NST receptor and transduction pathways have not yet been identified. We previously showed that N/OFQ inhibited [3H]5-hydroxytryptamine ([3H]5-HT) release from mouse cortical synaptosomes via activation of NOP receptors. We now investigate whether NST regulates [3H]5-HT release in the same preparation. Experimental approach: Mouse and rat cerebrocortical synaptosomes in superfusion, preloaded with [3H]5-HT and stimulated with 1 min pulses of 10 mM KCl, were used. Key results: Bovine NST (b-NST) inhibited the K+-induced [3H]5-HT release, displaying similar efficacy but lower potency than N/OFQ. b-NST action underwent concentration-dependent and time-dependent desensitization, and was not prevented either by the NOP receptor antagonist [Nphe1 Arg14,Lys15]N/OFQ(1-13)-NH2 (UFP-101) or by the non-selective opioid receptor antagonist, naloxone. Contrary to N/OFQ, b-NST reduced [3H]5-HT release from synaptosomes obtained from NOP receptor knockout mice. However, both N/OFQ and NST were ineffective in synaptosomes pre-treated with the Gi/o protein inhibitor, Pertussis toxin. NST-N/OFQ interactions were also investigated. Co-application of maximal concentrations of both peptides did not result in additive effects, whereas pre-application of maximal b-NST concentrations partially attenuated N/OFQ inhibition. Conclusions and implications: We conclude that b-NST inhibits [3H]5-HT release via activation of Gi/o protein linked pathways, not involving classical opioid receptors and the NOP receptor. The present data strengthen the view that b-NST is, per se, a biologically active peptide endowed with agonist activity. PMID:17618307

  3. Treadmill exercise alleviates stress-induced impairment of social interaction through 5-hydroxytryptamine 1A receptor activation in rats

    PubMed Central

    Kim, Tae-Woon; Lim, Baek-Vin; Kim, Kijeong; Seo, Jin-Hee; Kim, Chang-Ju

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase B (trkB), and cyclic adenosine monophosphate response element binding protein (CREB) have been suggested as the neurobiological risk factors causing depressive disorder. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of depression. We in-vestigated the effect of treadmill exercise on social interaction in relation with BDNF and 5-HT expressions following stress in rats. Stress was induced by applying inescapable 0.2 mA electric foot shock to the rats for 7 days. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 4 weeks. Social interaction test and western blot for BDNF, TrkB, pCREB, and 5-HT1A in the hippocampus were performed. The results indicate that the spend time with unfamiliar partner was decreased by stress, in contrast, treadmill exercise increased the spending time in the stress-induced rats. Expressions of BDNF, TrkB, and pCREB were decreased by stress, in contrast, treadmill exercise enhanced expressions of BDNF, TrkB, and pCREB in the stress-induced rats. In addition, 5-HT1A receptor expression was de-creased by stress, in contrast, treadmill exercise enhanced 5-HT1A expression in the stress-induced rats. In the present study, treadmill exercise alleviated stress-induced social interaction impairment through enhancing hippocampal plasticity and serotonergic function in the hippocampus. These effects of treadmill exercise are achieved through 5-HT1A receptor activation. PMID:26331133

  4. Anxiolytic effect and memory improvement in rats by antisense oligodeoxynucleotide to 5-hydroxytryptamine-2A precursor protein.

    PubMed

    Cohen, Hagit

    2005-01-01

    Serotonergic (5-hydroxytryptamine; 5-HT) mechanisms have been implicated in a number of physiological and pathophysiological processes including mood, anxiety, and cognitive functioning. Among the many 5-HT receptor subtypes, the 5-HT2A receptors (5-HT2A-R) seem to be of particular importance in mediating these effects, and they are prime targets for a variety of psychoactive substances-from hallucinogenic drugs, through atypical antipsychotics, to anxiolytics and antidepressants. Various selective 5-HT2A-R ligands induce different behavioral responses. To determine whether receptor downregulation is an essential part of anxiolytic action, levels of 5-HT2A receptors were manipulated in rats using a nonpharmacological approach-by the administration of an antisense oligodeoxynucleotide (ASODN) to 5-HT2A-R. Each ASODN was injected icv between two and five times at 24-hr intervals. Control rats received injections of either a scrambled oligodeoxynucleotide (ScrODN) or the vehicle only. On Day 6, anxiety-related behavior was assessed in the elevated plus maze paradigm and performance of memory tasks in the Morris water maze. Gene transcripts were measured by quantitative reverse transcription polymerase chain reaction (PCR). The results show that compared to vehicle and ScrODN control animals, icv 5-HT2A-R-ASODN administrations for 4 consecutive days (but not less) significantly decreased anxietylike behavior and improved memory retention performance. The reduction in anxiety-related behavior in 5-HT2A-R-ASODN rats was accompanied by a decrease in 5-HT2A-R-mRNA expression in the frontal cortex and in the hippocampus. Receptor downregulation has been proposed as one of the central mechanisms for anxiolytic drug actions. Antisense-mediated downmanipulation of receptors in this study, especially of 5-HT2A, supports this theory. PMID:16149040

  5. Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment.

    PubMed

    Huang, Xi-Ping; Setola, Vincent; Yadav, Prem N; Allen, John A; Rogan, Sarah C; Hanson, Bonnie J; Revankar, Chetana; Robers, Matt; Doucette, Chris; Roth, Bryan L

    2009-10-01

    Drug-induced valvular heart disease (VHD) is a serious side effect of a few medications, including some that are on the market. Pharmacological studies of VHD-associated medications (e.g., fenfluramine, pergolide, methysergide, and cabergoline) have revealed that they and/or their metabolites are potent 5-hydroxytryptamine(2B) (5-HT(2B)) receptor agonists. We have shown that activation of 5-HT(2B) receptors on human heart valve interstitial cells in vitro induces a proliferative response reminiscent of the fibrosis that typifies VHD. To identify current or future drugs that might induce VHD, we screened approximately 2200 U.S. Food and Drug Administration (FDA)-approved or investigational medications to identify 5-HT(2B) receptor agonists, using calcium-based high-throughput screening. Of these 2200 compounds, 27 were 5-HT(2B) receptor agonists (hits); 14 of these had previously been identified as 5-HT(2B) receptor agonists, including seven bona fide valvulopathogens. Six of the hits (guanfacine, quinidine, xylometazoline, oxymetazoline, fenoldopam, and ropinirole) are approved medications. Twenty-three of the hits were then "functionally profiled" (i.e., assayed in parallel for 5-HT(2B) receptor agonism using multiple readouts to test for functional selectivity). In these assays, the known valvulopathogens were efficacious at concentrations as low as 30 nM, whereas the other compounds were less so. Hierarchical clustering analysis of the pEC(50) data revealed that ropinirole (which is not associated with valvulopathy) was clearly segregated from known valvulopathogens. Taken together, our data demonstrate that patterns of 5-HT(2B) receptor functional selectivity might be useful for identifying compounds likely to induce valvular heart disease. PMID:19570945

  6. Reduced sensitivity to both positive and negative reinforcement in mice over-expressing the 5-hydroxytryptamine transporter.

    PubMed

    Line, Samantha J; Barkus, Chris; Rawlings, Nancy; Jennings, Katie; McHugh, Stephen; Sharp, Trevor; Bannerman, David M

    2014-12-01

    The 5-hydroxytryptamine (5-HT) transporter (5-HTT) is believed to play a key role in both normal and pathological psychological states. Much previous data suggest that the s allele of the polymorphic regulatory region of the 5-HTT gene promoter is associated with reduced 5-HTT expression and vulnerability to psychiatric disorders, including anxiety and depression. In comparison, the l allele, which increases 5-HTT expression, is generally considered protective. However, recent data link this allele to both abnormal 5-HT signalling and psychopathic traits. Here, we studied the processing of aversive and rewarding cues in transgenic mice that over-express the 5-HTT (5-HTTOE mice). Compared with wild-type mice, 5-HTTOE mice froze less in response to both a tone that had previously been paired with footshock, and the conditioning context. In addition, on a decision-making T-maze task, 5-HTTOE mice displayed reduced preference for a larger, delayed reward and increased preference for a smaller, immediate reward, suggesting increased impulsiveness compared with wild-type mice. However, further inspection of the data revealed that 5-HTTOE mice displayed a relative insensitivity to reward magnitude, irrespective of delay. In contrast, 5-HTTOE mice appeared normal on tests of spatial working and reference memory, which required an absolute choice between options associated with either reward or no reward. Overall, the present findings suggest that 5-HTT over-expression results in a reduced sensitivity to both positive and negative reinforcers. Thus, these data show that increased 5-HTT expression has some maladaptive effects, supporting recent suggestions that l allele homozygosity may be a potential risk factor for disabling psychiatric traits. PMID:25283165

  7. Synergistic effect of 5-hydroxytryptamine 3 and neurokinin 1 receptor antagonism in rodent models of somatic and visceral pain.

    PubMed

    Greenwood-Van Meerveld, Beverley; Mohammadi, Ehsan; Tyler, Karl; Pietra, Claudio; Bee, Lucy A; Dickenson, Anthony

    2014-10-01

    Synergistic activity has been observed between serotonergic 5-hydroxytryptamine 3 (5-HT3) and tachykinergic neurokinin 1 (NK1) receptor-mediated responses. This study investigated the efficacy of a 5-HT3 antagonist, palonosetron, and a NK1 antagonist, netupitant, alone or in combination in rodent models of somatic and visceral colonic hypersensitivity. In a rat model of experimental neuropathic pain, somatic hypersensitivity was quantified by the number of ipsilateral paw withdrawals to a von Frey filament (6g). Electrophysiologic responses were recorded in the dorsal horn neurons after mechanical or thermal stimuli. Acute colonic hypersensitivity was induced experimentally in rats by infusing dilute acetic acid (0.6%) directly into the colon. Colonic sensitivity was assessed by a visceromotor behavioral response quantified as the number of abdominal contractions in response to graded isobaric pressures (0-60 mm Hg) of colorectal distension. Palonosetron or netupitant was administered alone or in combination via oral gavage. When dosed alone, both significantly reduced somatic sensitivity, decreased the evoked response of spinal dorsal horn neurons to mechanical or thermal stimulation, and caused significant (P < 0.05) inhibition of colonic hypersensitivity in a dose-dependent manner. The combined administration of palonosetron and netupitant at doses that were ineffective alone significantly reduced both somatic and visceral sensitivity and decreased the evoked response of spinal dorsal horn neurons to mechanical or thermal stimulation. In summary, the combination of palonosetron with a NK1 receptor antagonist showed synergistic analgesic activity in rodent models of somatic and visceral hypersensitivity, and may prove to be a useful therapeutic approach to treat pain associated with irritable bowel syndrome. PMID:25077526

  8. Treadmill exercise alleviates stress-induced impairment of social interaction through 5-hydroxytryptamine 1A receptor activation in rats.

    PubMed

    Kim, Tae-Woon; Lim, Baek-Vin; Kim, Kijeong; Seo, Jin-Hee; Kim, Chang-Ju

    2015-08-01

    Brain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase B (trkB), and cyclic adenosine monophosphate response element binding protein (CREB) have been suggested as the neurobiological risk factors causing depressive disorder. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of depression. We in-vestigated the effect of treadmill exercise on social interaction in relation with BDNF and 5-HT expressions following stress in rats. Stress was induced by applying inescapable 0.2 mA electric foot shock to the rats for 7 days. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 4 weeks. Social interaction test and western blot for BDNF, TrkB, pCREB, and 5-HT1A in the hippocampus were performed. The results indicate that the spend time with unfamiliar partner was decreased by stress, in contrast, treadmill exercise increased the spending time in the stress-induced rats. Expressions of BDNF, TrkB, and pCREB were decreased by stress, in contrast, treadmill exercise enhanced expressions of BDNF, TrkB, and pCREB in the stress-induced rats. In addition, 5-HT1A receptor expression was de-creased by stress, in contrast, treadmill exercise enhanced 5-HT1A expression in the stress-induced rats. In the present study, treadmill exercise alleviated stress-induced social interaction impairment through enhancing hippocampal plasticity and serotonergic function in the hippocampus. These effects of treadmill exercise are achieved through 5-HT1A receptor activation. PMID:26331133

  9. Changes in 5-hydroxytryptamine and cortisol plasma levels in menopausal women after inhalation of clary sage oil.

    PubMed

    Lee, Kyung-Bok; Cho, Eun; Kang, Young-Sook

    2014-11-01

    The purpose of this study was to examine the antidepressant-like effects of clary sage oil on human beings by comparing the neurotransmitter level change in plasma. The voluntary participants were 22 menopausal women in 50's. Subjects were classified into normal and depression tendency groups using each of Korean version of Beck Depression Inventory-I (KBDI-I), KBDI-II, and Korean version of Self-rating Depression Scale. Then, the changes in neurotransmitter concentrations were compared between two groups. After inhalation of clary sage oil, cortisol levels were significantly decreased while 5-hydroxytryptamine (5-HT) concentration was significantly increased. Thyroid stimulating hormone was also reduced in all groups but not statistically significantly. The different change rate of 5-HT concentration between normal and depression tendency groups was variable according to the depression measurement inventory. When using KBDI-I and KBDI-II, 5-HT increased by 341% and 828% for the normal group and 484% and 257% for the depression tendency group, respectively. The change rate of cortisol was greater in depression tendency groups compared with normal groups, and this difference was statistically significant when using KBDI-II (31% vs. 16% reduction) and Self-rating Depression Scale inventory (36% vs. 8.3% reduction). Among three inventories, only KBDI-II differentiated normal and depression tendency groups with significantly different cortisol level. Finally, clary sage oil has antidepressant-like effect, and KBDI-II inventory may be the most sensitive and valid tool in screening for depression status or severity. PMID:24802524

  10. The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting

    PubMed Central

    Palli, Swetha Rao; Grabner, Michael; Quimbo, Ralph A; Rugo, Hope S

    2015-01-01

    Purpose To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. Materials and methods This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. Results We identified 1,832 palonosetron and 2,387 other 5-HT3 RA (“other”) patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Conclusion Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs. PMID:26124681

  11. Pharmacological profiles of presynaptic nociceptin/orphanin FQ receptors modulating 5-hydroxytryptamine and noradrenaline release in the rat neocortex

    PubMed Central

    Marti, Matteo; Stocchi, Sara; Paganini, Francesca; Mela, Flora; Risi, Carmela De; Calo', Girolamo; Guerrini, Remo; Barnes, Timothy A; Lambert, David G; Beani, Lorenzo; Bianchi, Clementina; Morari, Michele

    2003-01-01

    The pharmacological profiles of presynaptic nociceptin/orphanin FQ (N/OFQ) peptide receptors (NOP) modulating 5-hydroxytryptamine (5-HT) and noradrenaline (NE) release in the rat neocortex were characterized in a preparation of superfused synaptosomes challenged with 10 mM KCl. N/OFQ concentration-dependently inhibited K+-evoked [3H]-5-HT and [3H]-NE overflow with similar potency (pEC50 ∼7.9 and ∼7.7, respectively) and efficacy (maximal inhibition ∼40%). N/OFQ (0.1 μM) inhibition of [3H]-5-HT and [3H]-NE overflow was antagonized by selective NOP receptor antagonists of peptide ([Nphe1]N/OFQ(1-13)NH2 and UFP-101; 10 and 1 μM, respectively) and non-peptide (J-113397 and JTC-801; both 0.1 μM) nature. Antagonists were routinely applied 3 min before N/OFQ. However, a 21 min pre-application time was necessary for J-113397 and JTC-801 to prevent N/OFQ inhibition of [3H]-NE overflow. The NOP receptor ligand [Phe1ψ(CH2-NH)Gly2]N/OFQ(1-13)NH2 ([F/G]N/OFQ(1-13)NH2; 3 μM) did not affect K+-evoked [3H]-NE but inhibited K+-evoked [3H]-5-HT overflow in a UFP-101 sensitive manner. [F/G]N/OFQ(1-13)NH2 antagonized N/OFQ actions on both neurotransmitters. The time-dependency of JTC-801 action was studied in CHO cells expressing human NOP receptors. N/OFQ inhibited forskolin-stimulated cAMP accumulation and JTC-801, tested at different concentrations (0.1–10 μM) and pre-incubation times (0, 40 and 90 min), antagonized this effect in a time-dependent manner. The Schild-type analysis excluded a competitive type of antagonism. We conclude that presynaptic NO receptors inhibiting 5-HT and NE release in the rat neocortex have similar pharmacological profiles. Nevertheless, they can be differentiated pharmacologically on the basis of responsiveness to [F/G]N/OFQ(1-13)NH2 and time-dependent sensitivity towards non-peptide antagonists. PMID:12522077

  12. Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat

    NASA Technical Reports Server (NTRS)

    Lucot, J. B.

    1989-01-01

    5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.

  13. Prophylaxis of Radiation-Induced Nausea and Vomiting Using 5-Hydroxytryptamine-3 Serotonin Receptor Antagonists: A Systematic Review of Randomized Trials

    SciTech Connect

    Salvo, Nadia; Doble, Brett; Khan, Luluel; Amirthevasar, Gayathri; Dennis, Kristopher; Pasetka, Mark; DeAngelis, Carlo; Tsao, May; Chow, Edward

    2012-01-01

    Purpose: To systematically review the effectiveness and safety of 5-hydroxytryptamine-3 receptor antagonists (5-HT3 RAs) compared with other antiemetic medication or placebo for prophylaxis of radiation-induced nausea and vomiting. Methods and Materials: We searched the following electronic databases: MEDLINE, Embase, the Cochrane Central Register of Controlled Clinical Trials, and Web of Science. We also hand-searched reference lists of included studies. Randomized, controlled trials that compared a 5-HT3 RA with another antiemetic medication or placebo for preventing radiation-induced nausea and vomiting were included. We excluded studies recruiting patients receiving concomitant chemotherapy. When appropriate, meta-analysis was conducted using Review Manager (v5) software. Relative risks were calculated using inverse variance as the statistical method under a random-effects model. We assessed the quality of evidence by outcome using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Eligibility screening of 47 articles resulted in 9 included in the review. The overall methodologic quality was moderate. Meta-analysis of 5-HT3 RAs vs. placebo showed significant benefit for 5-HT3 RAs (relative risk [RR] 0.70; 95% confidence interval [CI] 0.57-0.86 for emesis; RR 0.84, 95% CI 0.73-0.96 for nausea). Meta-analysis comparing 5-HT3 RAs vs. metoclopramide showed a significant benefit of the 5-HT3 RAs for emetic control (RR 0.27, 95% CI 0.15-0.47). Conclusion: 5-Hydroxytryptamine-3 RAs are superior to placebo and other antiemetics for prevention of emesis, but little benefit was identified for nausea prevention. 5-Hydroxytryptamine-3 RAs are suggested for prevention of emesis. Limited evidence was found regarding delayed emesis, adverse events, quality of life, or need for rescue medication. Future randomized, controlled trials should evaluate different 5-HT3 antiemetics and new agents with novel mechanisms of action such at the NK

  14. Blockade of 5-hydroxytryptamine(3) receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat

    NASA Technical Reports Server (NTRS)

    Lucot, James B.

    1989-01-01

    The effects of the 5-hydroxytryptamine(3) (5-HT-3) antagonists ICS 205-930 and MDL 72222 on the emesis induced by motion or by emetic doses of xylazine (0.66 mg/kg administered SC) or cisplatin (7.5 mg/kg infused over a period of 4-5 min) were investigated in cats. It was found that neither the low (0.1 mg/kg) or the high (1.0 mg.kg) doses of ICS 205-930 or MDL 72222 prevented emesis elicited by screening motion challenges or xylazine. On the other hand, treatment cats by 1.0 mg/kg of ICS 205-930 was effective against cisplatin-induced motion sickness, in agreement with earlier results obtained on other mammals.

  15. Comparison of the performance of different DFT methods in the calculations of the molecular structure and vibration spectra of serotonin (5-hydroxytryptamine, 5-HT)

    NASA Astrophysics Data System (ADS)

    Yang, Yue; Gao, Hongwei

    2012-04-01

    Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter which plays an important role in treating acute or clinical stress. The comparative performance of different density functional theory (DFT) methods at various basis sets in predicting the molecular structure and vibration spectra of serotonin was reported. The calculation results of different methods including mPW1PW91, HCTH, SVWN, PBEPBE, B3PW91 and B3LYP with various basis sets including LANL2DZ, SDD, LANL2MB, 6-31G, 6-311++G and 6-311+G* were compared with the experimental data. It is remarkable that the SVWN/6-311++G and SVWN/6-311+G* levels afford the best quality to predict the structure of serotonin. The results also indicate that PBEPBE/LANL2DZ level show better performance in the vibration spectra prediction of serotonin than other DFT methods.

  16. Effects of p-chlorophenylalanine on the sensitivity of rat intestine to agonists and on intestinal 5-hydroxytryptamine levels during Nippostrongylus brasiliensis infection.

    PubMed Central

    Farmer, S. G.; Laniyonu, A. A.

    1984-01-01

    Infection of rats with the nematode N. brasiliensis caused non-specific increases in maximum response of isolated intestine to acetylcholine and 5-hydroxytryptamine (5-HT), and a specific subsensitivity to 5-HT. Intestinal levels of 5-HT, measured fluorimetrically, increased approximately 2 fold during infection. Treatment of infected rats with parachlorophenylalanine (PCPA) depleted the gut of 5-HT, and prevented the specific subsensitivity to the amine but not the increases in maximum response. Depletion of intestinal 5-HT did not prevent the immune expulsion of the parasites. It is concluded that the specific subsensitivity of the gut is due to the elevated levels of 5-HT during infection, but that the increased maximum responses are due to some other factor. Further, the lack of effect of PCPA on parasite rejection casts doubt on the proposed role of 5-HT in this process. PMID:6236863

  17. 5-hydroxytryptamine receptor (5-HT1DR) promotes colorectal cancer metastasis by regulating Axin1/β-catenin/MMP-7 signaling pathway

    PubMed Central

    Ji, Qing; Liu, Xuan; Zhou, Lihong; Song, Haiyan; Zhou, Xiqiu; Xu, Yangxian; Chen, Zhesheng; Cai, Jianfeng; Ji, Guang; Li, Qi

    2015-01-01

    Overexpression of 5-hydroxytryptamine (5-HT) in human cancer contributes to tumor metastasis, but the role of 5-HT receptor family in cancer has not been thoroughly explored. Here, we report overexpression of 5-HT1D receptor (5-HT1DR) was associated with Wnt signaling pathway and advanced tumor stage. The underlying mechanism of 5-HT1DR-promoted tumor invasion was through its activation on the Axin1/β-catenin/MMP-7 pathway. In an orthotopic colorectal cancer mouse model, we demonstrated that a 5-HT1DR antagonist (GR127935) effectively inhibited tumor metastasis through targeting Axin1. Furthermore, in intestinal epithelium cells, we observed that 5-HT1DR played an important role in cell invasion via Axin1/β-catenin/MMP-7 pathway. Together, our findings reveal an essential role of the physiologic level of 5-HT1DR in pulmonary metastasis of colorectal cancer. PMID:26214021

  18. A phase 1 randomized study evaluating the effect of omeprazole on the pharmacokinetics of a novel 5-hydroxytryptamine receptor 4 agonist, revexepride (SSP-002358), in healthy adults

    PubMed Central

    Pierce, David; Corcoran, Mary; Velinova, Maria; Hossack, Stuart; Hoppenbrouwers, Mieke; Martin, Patrick

    2015-01-01

    Background About 30% of patients with gastroesophageal reflux disease continue to experience symptoms despite treatment with proton pump inhibitors. The 5-hydroxytryptamine 4 receptor agonist revexepride (SSP-002358) is a novel prokinetic that stimulates gastrointestinal motility, which has been suggested as a continued cause of symptoms in these patients. The aim of this study was to assess whether revexepride pharmacokinetics were affected by co-administration of omeprazole, in preparation for a proof-of-concept evaluation of revexepride added to proton pump inhibitor treatment. Methods In this phase 1, open-label, randomized, two-period crossover study, healthy adults aged 18–55 years were given a single dose of revexepride 1 mg or revexepride 1 mg + omeprazole 40 mg. Pharmacokinetic parameters were assessed for up to 48 hours after administration of the investigational product. Adverse events, clinical chemistry and hematology parameters, electrocardiograms, and vital signs were monitored. Results In total, 42 participants were enrolled and 40 completed the study. The median age was 24 years (18–54 years), 55% were women and 93% were white. The pharmacokinetic parameters of revexepride were similar without or with omeprazole co-administration. The mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) was 23.3 ng · h/mL (standard deviation [SD]: 6.33 ng · h/mL) versus 24.6 ng · h/mL (SD: 6.31 ng · h/mL), and maximum plasma concentrations (Cmax) were 3.89 ng/mL (SD: 1.30 ng/mL) and 4.12 ng/mL (SD: 1.29 ng/mL) in participants without and with omeprazole, respectively. For AUC0–∞ and Cmax, the 90% confidence intervals for the ratios of geometric least-squares means (with:without omeprazole) were fully contained within the pre-defined equivalence limits of 0.80–1.25. Mean apparent terminal phase half-life was 9.95 hours (SD: 2.06 hours) without omeprazole, and 11.0 hours (SD: 3.25 hours) with omeprazole. Conclusion

  19. Depressive behavior and alterations in receptors for dopamine and 5-hydroxytryptamine in the brain of the senescence accelerated mouse (SAM)-P10.

    PubMed

    Onodera, T; Watanabe, R; Tha, K K; Hayashi, Y; Murayama, T; Okuma, Y; Ono, C; Oketani, Y; Hosokawa, M; Nomura, Y

    2000-08-01

    The senescence accelerated mouse (SAM) is known as a murine model of aging. SAM consists of senescence accelerated-prone mouse (SAMP) and senescence accelerated-resistant mouse (SAMR). Previous studies reported that SAMP10 exhibits age-related learning impairments and behavioral depression in a tail suspension test after 7 months. We investigated the changes in emotional behavior in a forced swimming test and in receptors for dopamine and 5-hydroxytryptamine (5-HT) in SAMP10. SAMP10 at 8 months showed an increase of immobility in the test compared with SAMR1. Treatment with desipramine (25 mg/kg, i.p., 3 days) in SAMP10 caused a decrease in immobility. In the cortex from SAMP10, [3H]quinpirole binding to D2/D3 dopamine receptors increased significantly compared with control SAMR1. In the hippocampus from SAMP10, [3H]8-hydroxy DPAT binding to 5-HT1A receptor increased. In midbrains from SAMP10, bindings of [3H]quinpirole and [3H]8-hydroxy DPAT increased. [3H]SCH23390 binding to D1/D5 receptors and [3H]ketanserin binding to 5-HT2 receptor in brain regions examined in SAMP10 were similar to those in SAMR1. The present findings represent the first neurochemical evidence of an increase of D2/D3 and 5-HT1A receptors in SAMP10. SAMP10 may be a useful model of aging associated depressive behavior. PMID:11001177

  20. Postnatal Treadmill Exercise Alleviates Prenatal Stress-Induced Anxiety in Offspring Rats by Enhancing Cell Proliferation Through 5-Hydroxytryptamine 1A Receptor Activation

    PubMed Central

    2016-01-01

    Purpose: Stress during pregnancy is a risk factor for the development of anxiety-related disorders in offspring later in life. The effects of treadmill exercise on anxiety-like behaviors and hippocampal cell proliferation were investigated using rats exposed to prenatal stress. Methods: Exposure of pregnant rats to a hunting dog in an enclosed room was used to induce stress. Anxiety-like behaviors of offspring were evaluated using the elevated plus maze test. Immunohistochemistry for the detection of 5-bromo-2ʹ- deoxyuridine and doublecortin (DCX) in the hippocampal dentate gyrus and 5-hydroxytryptamine 1A receptors (5-HT1A) in the dorsal raphe was conducted. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) levels in the hippocampus were evaluated by western blot analysis. Results: Offspring of maternal rats exposed to stress during pregnancy showed anxiety-like behaviors. Offspring also showed reduced expression of BDNF, TrkB, and DCX in the dentate gyrus, decreased cell proliferation in the hippocampus, and reduced 5-HT1A expression in the dorsal raphe. Postnatal treadmill exercise by offspring, but not maternal exercise during pregnancy, enhanced cell proliferation and expression of these proteins. Conclusions: Postnatal treadmill exercise ameliorated anxiety-like behaviors in offspring of stressed pregnant rats, and the alleviating effect of exercise on these behaviors is hypothesized to result from enhancement of cell proliferation through 5-HT1A activation in offspring rats. PMID:27230461

  1. Sensitive determination of norepinephrine, epinephrine, dopamine and 5-hydroxytryptamine by coupling HPLC with [Ag(HIO6 )2 ](5-) -luminol chemiluminescence detection.

    PubMed

    Wu, Dong; Xie, He; Lu, Haifeng; Li, Wei; Zhang, Qunlin

    2016-09-01

    Based on the enhancing effects of norepinephrine (NE), epinephrine (EP), dopamine (DA) and 5-hydroxytryptamine (5-HT) on the chemiluminescence (CL) reaction between [Ag(HIO6 )2 ](5-) and luminol in alkaline solution, a high-performance liquid chromatography (HPLC) method with CL detection was explored for the sensitive determination of monoamine neurotransmitters for the first time. The UV-visible absorption spectra were recorded to study the enhancement mechanism of monoamine neurotransmitters on the CL of [Ag(HIO6 )2 ](5-) and luminol reaction. The HPLC separation of NE, EP, DA and 5-HT was achieved with isocratic elution using a mixture of aqueous 0.2% phosphoric acid and methanol (5:95, v/v) within 11.0 min. Under the optimized conditions, the detection limits of NE, EP, DA, and 5-HT were 4.8, 0.9, 1.9 and 2.3 ng/mL, respectively, corresponding to 17.6-96.0 pg for 20 μL sample injection. The recoveries of monoamine neurotransmitters in rat brain were >95.6% with the precisions expressed by RSD <5.0%. The validated HPLC-CL method was successfully applied for the quantification of NE, EP, DA and 5-HT in rat brain. This method has promising potential for some biological and clinical investigations focusing on the levels of monoamine neurotransmitters. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26876580

  2. 5-hydroxytryptamine receptor (5-HT1DR) promotes colorectal cancer metastasis by regulating Axin1/β-catenin/MMP-7 signaling pathway.

    PubMed

    Sui, Hua; Xu, Hanchen; Ji, Qing; Liu, Xuan; Zhou, Lihong; Song, Haiyan; Zhou, Xiqiu; Xu, Yangxian; Chen, Zhesheng; Cai, Jianfeng; Ji, Guang; Li, Qi

    2015-09-22

    Overexpression of 5-hydroxytryptamine (5-HT) in human cancer contributes to tumor metastasis, but the role of 5-HT receptor family in cancer has not been thoroughly explored. Here, we report overexpression of 5-HT(1D) receptor (5-HT(1D)R) was associated with Wnt signaling pathway and advanced tumor stage. The underlying mechanism of 5-HT(1D)R-promoted tumor invasion was through its activation on the Axin1/β-catenin/MMP-7 pathway. In an orthotopic colorectal cancer mouse model, we demonstrated that a 5-HT(1D)R antagonist (GR127935) effectively inhibited tumor metastasis through targeting Axin1. Furthermore, in intestinal epithelium cells, we observed that 5-HT(1D)R played an important role in cell invasion via Axin1/β-catenin/MMP-7 pathway. Together, our findings reveal an essential role of the physiologic level of 5-HT(1D)R in pulmonary metastasis of colorectal cancer. PMID:26214021

  3. Regulation of Oligomeric Organization of the Serotonin 5-Hydroxytryptamine 2C (5-HT2C) Receptor Observed by Spatial Intensity Distribution Analysis*

    PubMed Central

    Ward, Richard J.; Pediani, John D.; Godin, Antoine G.; Milligan, Graeme

    2015-01-01

    The questions of whether G protein-coupled receptors exist as monomers, dimers, and/or oligomers and if these species interconvert in a ligand-dependent manner are among the most contentious current issues in biology. When employing spatial intensity distribution analysis to laser scanning confocal microscope images of cells stably expressing either a plasma membrane-associated form of monomeric enhanced green fluorescent protein (eGFP) or a tandem version of this fluorophore, the eGFP tandem was identified as a dimer. Similar studies on cells stably expressing an eGFP-tagged form of the epidermal growth factor receptor demonstrated that, although largely a monomer in the basal state, this receptor rapidly became predominantly dimeric upon the addition of its ligand epidermal growth factor. In cells induced to express an eGFP-tagged form of the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor, global analysis of construct quantal brightness was consistent with the predominant form of the receptor being dimeric. However, detailed spatial intensity distribution analysis demonstrated the presence of multiple forms ranging from monomers to higher-order oligomers. Furthermore, treatment with chemically distinct 5-HT2C receptor antagonists resulted in a time-dependent change in the quaternary organization to one in which there was a preponderance of receptor monomers. This antagonist-mediated effect was reversible, because washout of the ligand resulted in the regeneration of many of the oligomeric forms of the receptor. PMID:25825490

  4. A Chemocentric Informatics Approach to Drug Discovery: Identification and Experimental Validation of Selective Estrogen Receptor Modulators as ligands of 5-Hydroxytryptamine-6 Receptors and as Potential Cognition Enhancers

    PubMed Central

    Hajjo, Rima; Setola, Vincent; Roth, Bryan L.; Tropsha, Alexander

    2012-01-01

    We have devised a chemocentric informatics methodology for drug discovery integrating independent approaches to mining biomolecular databases. As a proof of concept, we have searched for novel putative cognition enhancers. First, we generated Quantitative Structure- Activity Relationship (QSAR) models of compounds binding to 5-hydroxytryptamine-6 receptor (5HT6R), a known target for cognition enhancers, and employed these models for virtual screening to identify putative 5-HT6R actives. Second, we queried chemogenomics data from the Connectivity Map (http://www.broad.mit.edu/cmap/) with the gene expression profile signatures of Alzheimer’s disease patients to identify compounds putatively linked to the disease. Thirteen common hits were tested in 5-HT6R radioligand binding assays and ten were confirmed as actives. Four of them were known selective estrogen receptor modulators that were never reported as 5-HT6R ligands. Furthermore, nine of the confirmed actives were reported elsewhere to have memory-enhancing effects. The approaches discussed herein can be used broadly to identify novel drug-target-disease associations. PMID:22537153

  5. The action of SDZ 205,557 at 5-hydroxytryptamine (5-HT3 and 5-HT4) receptors.

    PubMed Central

    Eglen, R. M.; Alvarez, R.; Johnson, L. G.; Leung, E.; Wong, E. H.

    1993-01-01

    1. The interaction of the novel antagonist, SDZ 205,557 (2-methoxy-4-amino-5-chloro benzoic acid 2-(diethylamino) ethyl ester), at 5-HT3 and 5-HT4 receptors has been assessed in vitro and in vivo. 2. In guinea-pig hippocampus and in the presence of 0.4 microM 5-carboxamidotryptamine, 5-HT4-mediated stimulation of adenylyl cyclase was competitively antagonized by SDZ 205,557, with a pA2 value of 7.5, and a Schild slope of 0.81. In rat carbachol-contracted oesophagus, 5-HT4-receptor mediated relaxations were surmountably antagonized by SDZ 205,557 with a similar pA2 value (7.3). This value was agonist-independent with the exception of (R)-zacopride, against which a significantly lower value (6.4) was observed. 3. In functional studies of 5-HT3 receptors, SDZ 205,557 exhibited an affinity of 6.2 in guinea-pig ileum compared with 6.9 at binding sites labelled by [3H]-quipazine in NG108-15 cells. In the anaesthetized, vagotomized micropig, SDZ 205,557 produced only a transient blockade of 5-HT4-mediated tachycardia. This contrasted with tropisetron, which was active for over 60 min after administration. The half-lives for the inhibitory responses of SDZ 205,557 and tropisetron were 23 and 116 min, respectively. 4. In conclusion, SDZ 205,557 has similar affinity for 5-HT3 and 5-HT4 receptors. The apparent selectivity observed in guinea-pig is due to the atypical nature of the 5-HT3 receptor in this species. The short duration of action of this novel antagonist may complicate its use in vivo. SDZ 205,557 should, therefore, be used with appropriate caution in studies defining the 5-HT4 receptor. PMID:8448587

  6. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine

    SciTech Connect

    McKenna, D.J.; Guan, X.M.; Shulgin, A.T. )

    1991-03-01

    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives {plus minus}fenfluramine, {plus minus}norfenfluramine, {plus minus}MDE, {plus minus}PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners.

  7. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine.

    PubMed

    McKenna, D J; Guan, X M; Shulgin, A T

    1991-03-01

    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives (+/-)fenfluramine, (+/-)norfenfluramine, (+/-)MDE, (+/-)PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners. PMID:1829838

  8. Involvement of N-methyl-d-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test.

    PubMed

    Kordjazy, Nastaran; Haj-Mirzaian, Arya; Amiri, Shayan; Ostadhadi, Sattar; Amini-Khoei, Hossein; Dehpour, Ahmad Reza

    2016-02-01

    Recent evidence indicates that 5-hydroxytryptamine 3 (5-HT3) antagonists such as ondansetron and tropisetron exert positive behavioral effects in animal models of depression. Due to the ionotropic nature of 5-HT3 and N-methyl-d-aspartate (NMDA) receptors, plus their contribution to the pathophysiology of depression, we investigated the possible role of NMDA receptors in the antidepressant-like effect of 5-HT3 receptor antagonists in male mice. In order to evaluate the animals' behavior in response to different treatments, we performed open-field test (OFT), forced swimming test (FST), and tail-suspension test (TST), which are considered as valid tasks for measuring locomotor activity and depressive-like behaviors in mice. Our data revealed that intraperitoneal (i.p.) administration of tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01, and 0.1μg/kg) significantly decreased the immobility time in FST and TST. Also, co-administration of subeffective doses of tropisetron (1mg/kg, i.p.) or ondansetron (0.001μg/kg, i.p.) with subeffective doses of NMDA receptor antagonists, ketamine (1mg/kg, i.p.), MK-801 (0.05mg/kg, i.p.) and magnesium sulfate (10mg/kg, i.p.) resulted in a reduced immobility time both in FST and TST. The subeffective dose of NMDA (NMDA receptor agonist, 75mg/kg, i.p.) abolished the effects of 5-HT3 antagonists in FST and TST, further supporting the presumed interaction between 5-HT3 and NMDA receptors. These treatments did not affect the locomotor behavior of animals in OFT. Finally, the results of our study suggest that the positive effects of 5-HT3 antagonists on the coping behavior of mice in FST and TST are at least partly mediated through NMDA receptors participation. PMID:26604075

  9. 5-Hydroxytryptamine 1A receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception.

    PubMed

    Biagioni, Audrey Franceschi; de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; da Silva, Juliana Almeida; dos Anjos-Garcia, Tayllon; Roncon, Camila Marroni; Corrado, Alexandre Pinto; Zangrossi, Hélio; Coimbra, Norberto Cysne

    2016-03-01

    The dorsal raphe nucleus (DRN) is an important brainstem source of 5-hydroxytryptamine (5-HT), and 5-HT plays a key role in the regulation of panic attacks. The aim of the present study was to determine whether 5-HT1A receptor-containing neurons in the medial hypothalamus (MH) receive neural projections from DRN and to then determine the role of this neural substrate in defensive responses. The neurotracer biotinylated dextran amine (BDA) was iontophoretically microinjected into the DRN, and immunohistochemical approaches were then used to identify 5HT1A receptor-labelled neurons in the MH. Moreover, the effects of pre-treatment of the dorsomedial hypothalamus (DMH) with 8-OH-DPAT and WAY-100635, a 5-HT1A receptor agonist and antagonist, respectively, followed by local microinjections of bicuculline, a GABAA receptor antagonist, were investigated. We found that there are many projections from the DRN to the perifornical lateral hypothalamus (PeFLH) but also to DMH and ventromedial (VMH) nuclei, reaching 5HT1A receptor-labelled perikarya. DMH GABAA receptor blockade elicited defensive responses that were followed by antinociception. DMH treatment with 8-OH-DPAT decreased escape responses, which strongly suggests that the 5-HT1A receptor modulates the defensive responses. However, DMH treatment with WAY-100635 failed to alter bicuculline-induced defensive responses, suggesting that 5-HT exerts a phasic influence on 5-HT1A DMH neurons. The activation of the inhibitory 5-HT1A receptor had no effect on antinociception. However, blockade of the 5-HT1A receptor decreased fear-induced antinociception. The present data suggest that the ascending pathways from the DRN to the DMH modulate panic-like defensive behaviours and mediate antinociceptive phenomenon by recruiting 5-HT1A receptor in the MH. PMID:26749090

  10. A comparison of the effects of chlorpromazine and more selective histamine and 5-hydroxytryptamine antagonists on human IgG synthesis in vitro.

    PubMed

    Martinez, F; Coleman, J W

    1990-01-01

    We have shown previously that chlorpromazine, a drug associated with immunological abnormalities in vivo, significantly potentiates pokeweed mitogen (PWM)-stimulated IgG synthesis by human peripheral blood mononuclear cells (PBMC) in culture. Chlorpromazine is a pharmacological antagonist of histamine and 5-hydroxytryptamine (5-HT) and thus may exert its immune-enhancing effects by competing with these amines for their respective receptors, which are known to be present on lymphocytes. In this report we show that histamine and 5-HT are present at micromolar concentrations in PBMC cultures. To examine the role of histamine and 5-HT in chlorpromazine-induced enhancement of IgG synthesis we incubated PWM-treated cells with a range of selective histamine and 5-HT antagonists, and with the amines added to cultures either alone or in combination with chlorpromazine. The H1 antagonists mepyramine and promethazine and the H2 antagonist cimetidine had no significant effect on IgG synthesis. The combined 5-HT1/5-HT2 antagonists methysergide and methiothepin also failed to modulate synthesis. Neither histamine nor 5-HT at concentrations up to 100 microM modulated IgG synthesis, nor did they abrogate the enhancement of IgG synthesis induced by chlorpromazine. We conclude that the modulation of IgG synthesis in vitro by chlorpromazine cannot be attributed to an interaction of this drug with lymphocyte receptors for histamine and 5-HT. Other possibilities for the mechanism of action of this drug on immune function are discussed. PMID:2329012

  11. Emetic responses to T-2 toxin, HT-2 toxin and emetine correspond to plasma elevations of peptide YY3-36 and 5-hydroxytryptamine.

    PubMed

    Wu, Wenda; Zhou, Hui-Ren; Bursian, Steven J; Link, Jane E; Pestka, James J

    2016-04-01

    Trichothecene mycotoxins are a family of potent translational inhibitors that are associated with foodborne outbreaks of human and animal gastroenteritis in which vomiting is a clinical hallmark. Deoxynivalenol (DON, vomitoxin) and other Type B trichothecenes have been previously demonstrated to cause emesis in the mink (Neovison vison), and this response has been directly linked to secretion of both the satiety hormone peptide YY3-36 (PYY3-36) and neurotransmitter 5-hydroxytryptamine (5-HT). Here, we characterized the emetic responses in the mink to T-2 toxin (T-2) and HT-2 toxin (HT-2), two highly toxic Type A trichothecenes that contaminate cereals, and further compared these effects to those of emetine, a natural alkaloid that is used medicinally and also well known to block translation and cause vomiting. Following intraperitoneal (IP) and oral exposure, all three agents caused vomiting with evident dose-dependent increases in both duration and number of emetic events as well as decreases in latency to emesis. T-2 and HT-2 doses causing emesis in 50 % of treated animals (ED50s) were 0.05 and 0.02 mg/kg BW following IP and oral administration, respectively, whereas the ED50s for emetine were 2.0 and 1.0 mg/kg BW for IP and oral exposure, respectively. Importantly, oral administration of all three toxins elicited marked elevations in plasma concentrations of PYY3-36 and 5-HT that corresponded to emesis. Taken together, the results suggest that T-2 and HT-2 were much more potent than emetine and that emesis induction by all three translational inhibitors co-occurred with increases in circulating levels of PYY3-36 and 5-HT. PMID:25855062

  12. Selective Recognition of 5-Hydroxytryptamine and Dopamine on a Multi-Walled Carbon Nanotube-Chitosan Hybrid Film-Modified Microelectrode Array

    PubMed Central

    Xu, Huiren; Wang, Li; Luo, Jinping; Song, Yilin; Liu, Juntao; Zhang, Song; Cai, Xinxia

    2015-01-01

    It is difficult to determine dopamine (DA) and 5-hydroxytryptamine (5-HT) accurately because of the interference of ascorbic acid (AA) in vitro, which has a high concentration and can be oxidized at a potential close to DA and 5-HT at a conventional electrode, combined with the overlapping voltammetric signal of DA and 5-HT at a bare electrode. Herein, chitosan (CS) was used as a stabilizing matrix by electrochemical reaction, and multi-walled carbon nanotubes (MWCNTs) were modified onto the microelectrode array (MEA). The CS-MWCNT hybrid film-modified MEA was quite effective at simultaneously recognizing these species in a mixture and resolved the overlapping anodic peaks of AA, DA and 5-HT into three well-defined oxidation peaks in differential pulse voltammetry (DPV) at −80 mV, 105 mV and 300 mV (versus Ag|AgCl), respectively. The linear responses were obtained in the range of 5 × 10−6 M to 2 × 10−4 M for DA (r = 0.996) and in the range of 1 × 10−5 M to 3 × 10−4 M for 5-HT (r = 0.999) using the DPV under the presence of a single substance. While DA coexisted with 5-HT in the interference of 3 × 10−4 M AA, the linear responses were obtained in the range of 1 × 10−5 M to 3 × 10−4 M for selective molecular recognition of DA (r = 0.997) and 5-HT (r = 0.997) using the DPV. Therefore, this proposed MEA was successfully used for selective molecular recognition and determination of DA and 5-HT using the DPV, which has a potential application for real-time determination in vitro experiments. PMID:25580900

  13. Prevention of 5-hydroxytryptamine2C receptor RNA editing and alternate splicing in C57BL/6 mice activates the hypothalamic-pituitary-adrenal axis and alters mood

    PubMed Central

    Bombail, Vincent; Qing, Wei; Chapman, Karen E; Holmes, Megan C

    2014-01-01

    The 5-hydroxytryptamine2C (5-HT)2C receptor is widely implicated in the aetiology of affective and eating disorders as well as regulation of the hypothalamo-pituitary-adrenal axis. Signalling through this receptor is regulated by A-to-I RNA editing, affecting three amino acids in the protein sequence, with unedited transcripts encoding a receptor (INI) that, in vitro, is hyperactive compared with edited isoforms. Targeted alteration (knock-in) of the Htr2c gene to generate ‘INI’ mice with no alternate splicing, solely expressing the full-length unedited isoform, did not produce an overt metabolic phenotype or altered anxiety behaviour, but did display reduced depressive-like and fear-associated behaviours. INI mice exhibited a hyperactive hypothalamo-pituitary-adrenal axis, with increased nadir plasma corticosterone and corticotrophin-releasing hormone expression in the hypothalamus but responded normally to chronic stress and showed normal circadian activity and activity in a novel environment. The circadian patterns of 5-HT2C receptor mRNA and mbii52, a snoRNA known to regulate RNA editing and RNA splicing of 5-HT2C receptor pre-mRNA, were altered in INI mice compared with wild-type control mice. Moreover, levels of 5-HT1A receptor mRNA were increased in the hippocampus of INI mice. These gene expression changes may underpin the neuroendocrine and behavioural changes observed in INI mice. However, the phenotype of INI mice was not consistent with a globally hyperactive INI receptor encoded by the unedited transcript in the absence of alternate splicing. Hence, the in vivo outcome of RNA editing may be neuronal cell type specific. PMID:25257581

  14. Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1A sequences.

    PubMed

    Li, Qian; Holmes, Andrew; Ma, Li; Van de Kar, Louis D; Garcia, Francisca; Murphy, Dennis L

    2004-12-01

    Our previous studies found that serotonin transporter (SERT) knock-out mice showed increased sensitivity to minor stress and increased anxiety-like behavior but reduced locomotor activity. These mice also showed decreased density of 5-hydroxytryptamine (5-HT1A) receptors in the hypothalamus, amygdala, and dorsal raphe. To evaluate the contribution of hypothalamic 5-HT1A receptors to these phenotypes of SERT knock-out mice, two studies were conducted. Recombinant adenoviruses containing 5-HT1A sense and antisense sequences (Ad-1AP-sense and Ad-1AP-antisense) were used to manipulate 5-HT1A receptors in the hypothalamus. The expression of the 5-HT1A genes is controlled by the 5-HT1A promoter, so that they are only expressed in 5-HT1A receptor-containing cells. (1) Injection of Ad-1AP-sense into the hypothalamus of SERT knock-out mice restored 5-HT1A receptors in the medial hypothalamus; this effect was accompanied by elimination of the exaggerated adrenocorticotropin responses to a saline injection (minor stress) and reduced locomotor activity but not by a change in increased exploratory anxiety-like behavior. (2) To further confirm the observation in SERT-/- mice, Ad-1AP-antisense was injected into the hypothalamus of normal mice. The density and the function of 5-HT1A receptors in the medial hypothalamus were significantly reduced in Ad-1AP-antisense-treated mice. Compared with the control group (injected with Ad-track), Ad-1A-antisense-treated mice showed a significant reduction in locomotor activity, but again no changes in exploratory anxiety-like behaviors, tested by elevated plus-maze and open-field tests. Thus, the present results demonstrate that medial hypothalamic 5-HT1A receptors regulate stress responses and locomotor activity but may not regulate exploratory anxiety-like behaviors. PMID:15574737

  15. Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors.

    PubMed

    Moya, Pablo R; Berg, Kelly A; Gutiérrez-Hernandez, Manuel A; Sáez-Briones, Patricio; Reyes-Parada, Miguel; Cassels, Bruce K; Clarke, William P

    2007-06-01

    2,5-Dimethoxy-4-substituted phenylisopropylamines and phenethylamines are 5-hydroxytryptamine (serotonin) (5-HT)(2A/2C) agonists. The former are partial to full agonists, whereas the latter are partial to weak agonists. However, most data come from studies analyzing phospholipase C (PLC)-mediated responses, although additional effectors [e.g., phospholipase A(2) (PLA(2))] are associated with these receptors. We compared two homologous series of phenylisopropylamines and phenethylamines measuring both PLA(2) and PLC responses in Chinese hamster ovary-K1 cells expressing human 5-HT(2A) or 5-HT(2C) receptors. In addition, we assayed both groups of compounds as head shake inducers in rats. At the 5-HT(2C) receptor, most compounds were partial agonists for both pathways. Relative efficacy of some phenylisopropylamines was higher for both responses compared with their phenethylamine counterparts, whereas for others, no differences were found. At the 5-HT(2A) receptor, most compounds behaved as partial agonists, but unlike findings at 5-HT(2C) receptors, all phenylisopropylamines were more efficacious than their phenethylamine counterparts. 2,5-Dimethoxyphenylisopropylamine activated only the PLC pathway at both receptor subtypes, 2,5-dimethoxyphenethylamine was selective for PLC at the 5-HT(2C) receptor, and 2,5-dimethoxy-4-nitrophenethylamine was PLA(2)-specific at the 5-HT(2A) receptor. For both receptors, the rank order of efficacy of compounds differed depending upon which response was measured. The phenylisopropylamines were strong head shake inducers, whereas their phenethylamine congeners were not, in agreement with in vitro results and the involvement of 5-HT(2A) receptors in the head shake response. Our results support the concept of functional selectivity and indicate that subtle changes in ligand structure can result in significant differences in the cellular signaling profile. PMID:17337633

  16. Cross-talk between 5-hydroxytryptamine and substance P in the melanogensis and apoptosis of B16F10 melanoma cells.

    PubMed

    Zhou, Jia; Geng, Kun-kun; Ping, Feng-feng; Gao, Yue-ying; Liu, Lei; Feng, Bai-nian

    2016-03-15

    Skin pigmentation is a complex process controlled by many different factors. Substance P (SP) regulates many biological functions, including melanogenesis and stress. Our previous study indicated that regulation of SP on melanocyte function was mediated by neurokinin 1 receptor (NK1 receptor). Substantial evidence has accumulated that psychological stress can be associated with skin pigmentation, so that the impact of 5-hydroxytryptamine (5-HT), one of the important factors participating in stress process, on melanogenesis has also been concerned. It has been reported that 5-HT induces melanin synthesis via 5-HT2A receptor. Furthermore, 5-HT2A receptor and NK1 receptor are G-protein coupled receptors (GPCRs) and both expressed on melanocyte, the present study was designed to investigate whether SP has influence on the adjustment function of 5-HT. Our data demonstrated that, SP inhibited 5-HT2A receptor expression to neutralize the pro-melanogenesis effect of 5-HT on B16F10 cells. The up-regulation of NK1 receptor expression was simultaneous with the down-regulation of 5-HT2A receptor treated by SP. This inhibition of 5-HT2A receptor expression by SP could be reversed by NK1 receptor antagonist Spantide I. Our studies indicated that SP could directly induce B16F10 cells apoptosis in vitro. 5-HT and 5-HT2A receptor agonist could mitigate this apoptotic effect of SP. It is the strong evidence of possible cross-talk between GPCRs and giving enlightenments when screening desirable drugs for target receptors. PMID:26872989

  17. Sucrose preload reduces snacking after mild mental stress in healthy participants as a function of 5-hydroxytryptamine transporter gene promoter polymorphism.

    PubMed

    Markus, C Rob; Jonkman, Lisa M; Capello, Aimee; Leinders, Sacha; Hüsch, Fabian

    2015-01-01

    Brain serotonin (5-hydroxytryptamine, 5-HT) dysfunction is considered to promote food intake and eating-related disturbances, especially under stress or negative mood. Vulnerability for 5-HT disturbances is considered to be genetically determined, including a short (S) allele polymorphism in the serotonin transporter gene (5-HTTLPR) that is associated with lower serotonin function. Since 5-HT function may be slightly increased by carbohydrate consumption, S-allele 5-HTTLPR carriers in particular may benefit from a sugar-preload due to their enhanced 5-HT vulnerability. The aim of the current study was to investigate whether a sugar-containing preload may reduce appetite and energy intake after exposure to stress to induce negative mood, depending on genetic 5-HT vulnerability. From a population of 771 healthy young male and female genotyped college students 31 S/S carriers (8 males, 23 females) and 26 long allele (L/L) carriers (9 males, 17 females) (mean ± S.D. 22 ± 1.6 years; body mass index, BMI, 18-33 kg/m(2)) were monitored for changes in appetite and snacking behavior after stress exposure. Results revealed an increased energy intake after mild mental stress (negative mood) mainly for high-fat sweet foods, which was significantly greater in S/S carriers, and only in these genotypes this intake was significantly reduced by a sucrose-containing preload. Although alternative explanations are possible, it is suggested that S/S participants may have enhanced brain (hypothalamic) 5-HT responsiveness to food that makes them more susceptible to the beneficial satiation effects of a sucrose-preload as well as to the negative effects of mild mental stress on weight gain. PMID:25423193

  18. Attenuation of phencyclidine-induced object recognition deficits by the combination of atypical antipsychotic drugs and pimavanserin (ACP 103), a 5-hydroxytryptamine(2A) receptor inverse agonist.

    PubMed

    Snigdha, S; Horiguchi, M; Huang, M; Li, Z; Shahid, M; Neill, J C; Meltzer, H Y

    2010-02-01

    Subchronic administration of the N-methyl-d-aspartate receptor antagonist, phencyclidine (PCP), in rodents has been shown to produce impairment in novel object recognition (NOR), a model of visual learning and memory. We tested the hypothesis that the selective 5-HT(2A) inverse agonists, pimavanserin and (R)-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl]-4-piperidinemethanol (M100907), would potentiate subeffective doses of atypical antipsychotic drugs (APDs) to reverse the NOR deficits. Female rats received vehicle or PCP (2 mg/kg b.i.d.) for 7 days, followed by a 7-day washout. Pimavanserin (3 mg/kg) or M100907 (1 mg/kg) alone, or four atypicial APDs, risperidone (0.05-0.1 mg/kg), melperone (1-3 mg/kg), olanzapine (1-2 mg/kg), or N-desmethylclozapine (1-2 mg/kg), and the typical APD, haloperidol (0.05-0.1 mg/kg), were administered alone, or in combination with pimavanserin or M100907, before NOR testing. The exploration times of objects during 3-min acquisition and retention trials, separated by a 1-min interval, were compared by analysis of variance. Vehicle-, but not PCP-treated, animals, explored the novel object significantly more than the familiar in the retention trial (p < 0.05-0.01). Pretreatment with the higher doses of the atypical APDs, but not pimavanserin, M100907, or haloperidol alone, reversed the effects of PCP. The effect of risperidone was blocked by haloperidol pretreatment. Coadministration of pimavanserin or M100907, with ineffective doses of the atypical APDs, but not haloperidol, also reversed the PCP-induced deficit in NOR. These results support the importance of 5-hydroxytryptamine(2A) receptor blockade relative to D(2) receptor blockade in the ability of atypicals to ameliorate the effect of subchronic PCP, a putative measure of cognitive dysfunction in schizophrenia. PMID:19864614

  19. Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT3A(b)) expressed in Xenopus laevis oocytes

    PubMed Central

    Mair, Ian D; Lambert, Jeremy J; Yang, Jay; Dempster, John; Peters, John A

    1998-01-01

    The present study has utilized the two electrode voltage-clamp technique to examine the pharmacological profile of a splice variant of the rat orthologue of the 5-hydroxytryptamine type 3A subunit (5-HT3A(b)) heterologously expressed in Xenopus laevis oocytes. At negative holding potentials, bath applied 5-HT (300 nM–10 μM) evoked a transient, concentration-dependent (EC50=1.1±0.1 μM), inward current. The response reversed in sign at a holding potential of −2.1±1.6 mV. The response to 5-HT was mimicked by the 5-HT3 receptor selective agonists 2-methyl-5-HT (EC50=4.1±0.2 μM), 1-phenylbiguanide (EC50=3.0±0.1 μM), 3-chlorophenylbiguanide (EC50=140± 10 nM), 3,5-dichlorophenylbiguanide (EC50=14.5±0.4 nM) and 2,5-dichlorophenylbiguanide (EC50= 10.2±0.6 nM). With the exception of 2-methyl-5-HT, all of the agonists tested elicited maximal current responses comparable to those produced by a saturating concentration (10 μM) of 5-HT. Responses evoked by 5-HT at EC50 were blocked by the 5-HT3 receptor selective antagonist ondansetron (IC50=231±22 pM) and by the less selective agents (+)-tubocurarine (IC50=31.9± 0.01 nM) and cocaine (IC50=2.1±0.2 μM). The data are discussed in the context of results previously obtained with the human and mouse orthologues of the 5-HT3A subunit. Overall, the study reinforces the conclusion that species differences detected for native 5-HT3 receptors extend to, and appear largely explained by, differences in the properties of homo-oligomeric receptors formed from 5-HT3A subunit orthologues. PMID:9756382

  20. A Meta-Analysis of the Effects of the 5-Hydroxytryptamine Transporter Gene-Linked Promoter Region Polymorphism on Susceptibility to Lifelong Premature Ejaculation

    PubMed Central

    Wu, Sheng; Shao, Hongbao; Dai, Feng; Peng, Tao; Qin, Feng; Feng, Ninghan

    2013-01-01

    Objective Premature ejaculation (PE) has been reported as the most common male sexual dysfunction with global prevalence rates estimated at approximately 30%. The neurobiogenesis of ejaculation is very complex and involves the serotoninergic (5-hydroxytryptamine, 5-HT) system. Recently, genetic polymorphisms located on SLC6A4 gene codifying for 5-HT transporter (5-HTT), the major regulator of serotonic neurotransmission, have been linked with the pathogenesis and risk of PE. Apparently studies of this type of polymorphism in PE have show conflicting results. Methods A meta-analysis was performed that are available in relation with 5-HTT gene-linked promoter region (5-HTTLPR) polymorphism and the risk of lifelong PE (LPE) in men to clarify this relationship. We searched Pubmed and Embase (last search updated on Aug 2012) using ‘premature ejaculation’, ‘polymorphism or variant’, ‘genotype’, ‘ejaculatory function’, and ‘rapid ejaculation’ as keywords and reference lists of studies corresponded to the inclusion criteria for meta-analysis. These studies involved the total number of 481 LPE men and 466 health control men subjects. Odds ratio (OR) and 95% confidence intervals (CIs) were used to evaluate this relationship. Results In the overall analysis, significant associations between LPE risk and 5-HTTLPR polymorphism were found (L-allele vs. S-allele OR = 0.86, 95% CI = 0.79–0.95, P = 0.002; LL vs. SS: OR = 0.80, 95% CI = 0.68–0.95, P = 0.009; LS vs. SS: OR = 0.85, 95% CI = 0.76–0.97, P = 0.012 and LL+LS vs. SS: OR = 0.88, 95% CI = 0.81–0.95, P = 0.002). Moreover, in subgroup analysis based on ethnicity, similar significant associations were detected. The Egger’s test did not reveal presence of a publication bias. Conclusions Our investigations demonstrate that 5-HTTLPR (L>S) polymorphism might protect men against LPE risk. Further studies based on larger sample size and gene

  1. Importance of inositol (1,4,5)-trisphosphate, intracellular Ca2+ release and myofilament Ca2+ sensitization in 5-hydroxytryptamine-evoked contraction of rabbit mesenteric artery.

    PubMed Central

    Seager, J. M.; Murphy, T. V.; Garland, C. J.

    1994-01-01

    1. Small strips from third-order branches of rabbit mesenteric artery (approximately 150-200 microM wide) contracted in response to noradrenaline (10 microM) or 5-hydroxytryptamine (5-HT; 10 microM) in oxygenated Krebs solution containing 2.5 mM Ca2+. In a Ca(2+)-free mock intracellular solution (0 Ca2+ plus 0.2 mM EGTA), noradrenaline (10 microM) and caffeine (10 mM) induced only a single, transient contraction in artery strips, while 5-HT (10 microM) failed to induce any response. 2. In strips of mesenteric artery which had been permeabilized with Staphylococcus alpha-toxin and bathed in Ca(2+)-free mock intracellular solution, noradrenaline (10 microM), caffeine (10 mM) and D-myo-inositol (1,4,5)-trisphosphate (IP3, 100 microM), but not 5-HT (10 or 100 microM) induced a transient contraction. In contrast to the non-permeabilized strips, contractions to noradrenaline, caffeine and IP3 were restored by prior incubation (10 min) in solution containing 0.08 microM Ca2+. The contractions to noradrenaline and IP3 in permeabilized muscle strips required the presence of 100 microM guanosine 5'-triphosphate (GTP), although in the absence of Ca2+. GTP alone did not induce contraction. 3. Exposure of permeabilized mesenteric artery strips to IP3 significantly reduced the subsequent contractile responses to caffeine. Contractile responses to caffeine and IP3 were abolished by the Ca(2+)-ATPase inhibitor, thapsigargin (1 microM). 4. Ca2+ (0.1-10 microM) induced concentration-dependent contraction in permeabilized artery strips. In strips which were submaximally contracted with 0.5 microM Ca2+/100 microM GTP, the subsequent addition of 5-HT (10 microM) stimulated further contraction. The protein kinase C inhibitor, H-7 (1 microM) abolished the 5-HT/GTP-induced contraction, but did not alter the contraction to Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8004397

  2. 5-Hydroxytryptamine(1F) receptors do not participate in vasoconstriction: lack of vasoconstriction to LY344864, a selective serotonin(1F) receptor agonist in rabbit saphenous vein.

    PubMed

    Cohen, M L; Schenck, K

    1999-09-01

    Recently, several novel approaches to the treatment of migraine have been advanced, including selective 5-hydroxytryptamine (or serotonin) 1B/1D (5-HT(1B/1D)) receptor agonists such as sumatriptan and 5-HT(1F) receptor agonists such as LY344864. Many 5-HT(1B/1D) receptor agonists have been identified based on their ability to produce cerebral vascular contraction, whereas LY344864 was identified as an inhibitor of trigeminal nerve-mediated dural extravasation. In our study, several triptan derivatives were compared with LY344864 for their ability to contract the rabbit saphenous vein, a tissue used in the preclinical identification of sumatriptan-related agonists. Sumatriptan, zolmitriptan, rizatriptan, and naratriptan all contracted the rabbit saphenous vein from baseline tone, whereas LY344864 in concentrations up to 10(-4) M did not contract the rabbit saphenous vein. Furthermore, vascular contractions to sumatriptan were markedly augmented in the presence of prostaglandin F(2alpha) (PGF(2alpha)). However, even in the presence of PGF(2alpha) (3 x 10(-7) M), LY344864 did not contract the rabbit saphenous vein in concentrations well in excess of its 5-HT(1F) receptor affinity (pK(i) = 8.2). Only when concentrations exceeded those likely to activate 5-HT(1B) and 5-HT(1D) receptors (>10(-5) M) did modest contractile responses occur in the presence of PGF(2alpha). Use of these serotonergic agonists revealed a significant correlation between the contractile potency in the rabbit saphenous vein and the affinities of these agonists at 5-HT(1B) and 5-HT(1D) receptors, although contractile agonist potencies were not quantitatively similar to 5-HT(1B) or 5-HT(1D) receptor affinities. In contrast, no significant correlation existed between the contractile potencies of these serotonergic agonists in the rabbit saphenous vein and their affinity at 5-HT(1F) receptors. These data support the contention that activation of 5-HT(1F) receptors will not result in vascular

  3. Autoradiographic localization of adenosine uptake sites in rat brain using (/sup 3/H)nitrobenzylthioinosine

    SciTech Connect

    Bisserbe, J.C.; Patel, J.; Marangos, P.J.

    1985-02-01

    The adenosine uptake site has been localized in rat brain by an in vitro light microscopic autoradiographic method, using (/sup 3/H)nitrobenzylthioinosine ((/sup 3/H)NBI) as the probe. The binding characteristics of (/sup 3/H)NBI on slide-mounted sections are comparable to those seen in studies performed on brain homogenates. A very high density of uptake sites occurs in the nucleus tractus solitarius, in the superficial layer of the superior colliculus, in several thalamic nuclei, and also in geniculate body nuclei. A high density of sites are also observed in the nucleus accumbens, the caudate putamen, the dorsal tegmentum area, the substantia nigra, and the central gray. The localization of the adenosine uptake site in brain may provide information on the functional activity of the site and suggests the involvement of the adenosine system in the central regulation of cardiovascular function.

  4. Dopamine uptake sites in the striatum are distributed differentially in striosome and matrix compartments

    SciTech Connect

    Graybiel, A.M.; Moratalla, R. )

    1989-11-01

    A major mechanism of neurotransmitter inactivation at catecholaminergic synapses in reuptake of released transmitter at high-affinity uptake sites on presynaptic terminals. The authors have analyzed the anatomical distribution of site-selective ligand binding for dopamine uptake sites in the striatum of rat, cat, and monkey. The authors report here that desipramine-sensitive ({sup 3}H)mazindol binding sites have highly heterogeneous distributions in the dorsal and the ventral striatum. In the caudate nucleus of cat and monkey, ({sup 3}H)mazindol binding observes striosomal ordering, being reduced in striosomes and heightened in the extrastriosomal matrix. Some local heterogeneity appears in the ventral caudoputamen of the rat. Different subdivisions of the nucleus accumbens also have different binding levels. These findings suggest that some functional effects of psychoactive drugs, such as cocaine, and that bind to the dopamine-uptake complex could be related to the distribution of these specific uptake sites. The findings also raise the possibility that these distributions could result in selective neuronal vulnerability to neurotoxins, such as 1-methyl-4-phenylpyridine (MPP{sup +}), that depend on the dopamine-uptake complex for entry into neurons.

  5. Prion Uptake in the Gut: Identification of the First Uptake and Replication Sites

    PubMed Central

    Kujala, Pekka; Raymond, Claudine R.; Romeijn, Martijn; Godsave, Susan F.; van Kasteren, Sander I.; Wille, Holger; Prusiner, Stanley B.; Mabbott, Neil A.; Peters, Peter J.

    2011-01-01

    After oral exposure, prions are thought to enter Peyer's patches via M cells and accumulate first upon follicular dendritic cells (FDCs) before spreading to the nervous system. How prions are actually initially acquired from the gut lumen is not known. Using high-resolution immunofluorescence and cryo-immunogold electron microscopy, we report the trafficking of the prion protein (PrP) toward Peyer's patches of wild-type and PrP-deficient mice. PrP was transiently detectable at 1 day post feeding (dpf) within large multivesicular LAMP1-positive endosomes of enterocytes in the follicle-associated epithelium (FAE) and at much lower levels within M cells. Subsequently, PrP was detected on vesicles in the late endosomal compartments of macrophages in the subepithelial dome. At 7–21 dpf, increased PrP labelling was observed on the plasma membranes of FDCs in germinal centres of Peyer's patches from wild-type mice only, identifying FDCs as the first sites of PrP conversion and replication. Detection of PrP on extracellular vesicles displaying FAE enterocyte-derived A33 protein implied transport towards FDCs in association with FAE-derived vesicles. By 21 dpf, PrP was observed on the plasma membranes of neurons within neighbouring myenteric plexi. Together, these data identify a novel potential M cell-independent mechanism for prion transport, mediated by FAE enterocytes, which acts to initiate conversion and replication upon FDCs and subsequent infection of enteric nerves. PMID:22216002

  6. Prion uptake in the gut: identification of the first uptake and replication sites.

    PubMed

    Kujala, Pekka; Raymond, Claudine R; Romeijn, Martijn; Godsave, Susan F; van Kasteren, Sander I; Wille, Holger; Prusiner, Stanley B; Mabbott, Neil A; Peters, Peter J

    2011-12-01

    After oral exposure, prions are thought to enter Peyer's patches via M cells and accumulate first upon follicular dendritic cells (FDCs) before spreading to the nervous system. How prions are actually initially acquired from the gut lumen is not known. Using high-resolution immunofluorescence and cryo-immunogold electron microscopy, we report the trafficking of the prion protein (PrP) toward Peyer's patches of wild-type and PrP-deficient mice. PrP was transiently detectable at 1 day post feeding (dpf) within large multivesicular LAMP1-positive endosomes of enterocytes in the follicle-associated epithelium (FAE) and at much lower levels within M cells. Subsequently, PrP was detected on vesicles in the late endosomal compartments of macrophages in the subepithelial dome. At 7-21 dpf, increased PrP labelling was observed on the plasma membranes of FDCs in germinal centres of Peyer's patches from wild-type mice only, identifying FDCs as the first sites of PrP conversion and replication. Detection of PrP on extracellular vesicles displaying FAE enterocyte-derived A33 protein implied transport towards FDCs in association with FAE-derived vesicles. By 21 dpf, PrP was observed on the plasma membranes of neurons within neighbouring myenteric plexi. Together, these data identify a novel potential M cell-independent mechanism for prion transport, mediated by FAE enterocytes, which acts to initiate conversion and replication upon FDCs and subsequent infection of enteric nerves. PMID:22216002

  7. The atypical antipsychotic profile of NRA0045, a novel dopamine D4 and 5-hydroxytryptamine2A receptor antagonist, in rats

    PubMed Central

    Okuyama, Shigeru; Chaki, Shigeyuki; Kawashima, Naoya; Suzuki, Yoshiko; Ogawa, Shin-ichi; Kumagai, Toshihito; Nakazato, Atsuro; Nagamine, Masashi; Yamaguchi, Kazumasa; Tomisawa, Kazuyuki

    1997-01-01

    The atypical antipsychotic profile of (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl] thiazole (NRA0045), a potent dopamine D4 and 5-hydroxytryptamine (5-HT)2A receptor antagonist, was examined in rats. Spontaneous locomotor activity was decreased dose-dependently with i.p. administration of clozapine (ED50 3.7 mg kg−1), haloperidol (ED50 0.1 mg kg−1) and chlorpromazine (ED50 0.9 mg kg−1), whereas inhibition of this type of behaviour induced by i.p. administration of NRA0045, at doses up to 10 mg kg−1, did not exceed 50%. Locomotor hyperactivity induced by methamphetamine (MAP, 2 mg kg−1, i.p.) in rats (a model of antipsychotic activity) was dose-dependently antagonized by NRA0045 (ED50 0.4 mg kg−1, i.p., and 0.3 mg kg−1, p.o., respectively), clozapine (ED50 0.3 mg kg−1, i.p. and 0.8 mg kg−1, p.o., respectively), haloperidol (ED50 0.02 mg kg−1, i.p. and 0.1 mg kg−1, p.o., respectively), chlorpromazine (ED50 0.3 mg kg−1, i.p. and 3.3 mg kg−1, p.o., respectively). In contrast, the MAP (3 mg kg−1, i.v.)-induced stereotyped behaviour in rats (a model of extrapyramidal symptoms) was not affected by NRA0045 or clozapine, at the highest dose given (30 mg kg−1, i.p.). Haloperidol (ED50 0.3 mg kg−1, i.p.) and chlorpromazine (ED50 4.8 mg kg−1, i.p.) strongly blocked the MAP-induced stereotyped behaviour. NRA0045 and clozapine selectively blocked behaviour associated with activation of the mesolimbic/mesocortical dopamine neurones rather than nigrostriatal dopamine neurones. Extracellular single-unit recording studies demonstrated that MAP (1 mg kg−1, i.v.) decreased the firing rate in the substantia nigra (A9) and ventral tegmental area (A10) dopamine neurones in anaesthetized rats. NRA0045 completely reversed the inhibitory effects of MAP on A10 dopamine neurones (ED50 0.1 mg kg−1, i.v.), whereas the inhibitory effects of

  8. Autoradiographic localization of /sup 3/H-paroxetine-labeled serotonin uptake sites in rat brain

    SciTech Connect

    De Souza, E.B.; Kuyatt, B.L.

    1987-01-01

    Paroxetine is a potent and selective inhibitor of serotonin uptake into neurons. Serotonin uptake sites have been identified, localized, and quantified in rat brain by autoradiography with 3H-paroxetine; 3H-paroxetine binding in slide-mounted sections of rat forebrain was of high affinity (KD = 10 pM) and the inhibition affinity constant (Ki) values of various drugs in competing 3H-paroxetine binding significantly correlated with their reported potencies in inhibiting synaptosomal serotonin uptake. Serotonin uptake sites labeled by 3H-paroxetine were highly concentrated in the dorsal and median raphe nuclei, central gray, superficial layer of the superior colliculus, lateral septal nucleus, paraventricular nucleus of the thalamus, and the islands of Calleja. High concentrations of 3H-paroxetine binding sites were found in brainstem areas containing dopamine (substantia nigra and ventral tegmental area) and norepinephrine (locus coeruleus) cell bodies. Moderate concentrations of 3H-paroxetine binding sites were present in laminae I and IV of the frontal parietal cortex, primary olfactory cortex, olfactory tubercle, regions of the basal ganglia, septum, amygdala, thalamus, hypothalamus, hippocampus, and some brainstem areas including the interpeduncular, trigeminal, and parabrachial nuclei. Lower densities of 3H-paroxetine binding sites were found in other regions of the neocortex and very low to nonsignificant levels of binding were present in white matter tracts and in the cerebellum. Lesioning of serotonin neurons with 3,4-methylenedioxyamphetamine caused large decreases in 3H-paroxetine binding. The autoradiographic distribution of 3H-paroxetine binding sites in rat brain corresponds extremely well to the distribution of serotonin terminals and cell bodies as well as with the pharmacological sites of action of serotonin.

  9. Uptake of HIV testing in substance use disorder treatment programs that offer on-site testing.

    PubMed

    Kyle, Tiffany L; Horigian, Viviana E; Tross, Susan; Gruber, Valerie A; Pereyra, Margaret; Mandler, Raul N; Feaster, Daniel J; Metsch, Lisa R

    2015-03-01

    Increasing rates of HIV testing within substance use disorder (SUD) treatment clients is an important public health strategy for reducing HIV transmission rates. The present study examined uptake of HIV testing among 1,224 clients in five SUD treatment units that offered on-site testing in Florida, New York, and California. Nearly one-third (30 %) of the participants, who had not previously tested positive, reported not having been tested for HIV within the past 12 months. Women, African Americans, and injection drug users had a higher likelihood of having been tested within the past 12 months. The SUD treatment program was the most frequently identified location of participants' last HIV test. Despite the availability of free, on-site testing, a substantial proportion of clients were not tested, suggesting that strategies to increase uptake of testing should include addressing barriers not limited to location and cost. PMID:25074737

  10. Native Plant Uptake Model for Radioactive Waste Disposal Areas at the Nevada Test Site

    SciTech Connect

    BROWN,THERESA J.; WIRTH,SHARON

    1999-09-01

    This report defines and defends the basic framework, methodology, and associated input parameters for modeling plant uptake of radionuclides for use in Performance Assessment (PA) activities of Radioactive Waste Management Sites (RWMS) at the Nevada Test Site (NTS). PAs are used to help determine whether waste disposal configurations meet applicable regulatory standards for the protection of human health, the environment, or both. Plants adapted to the arid climate of the NTS are able to rapidly capture infiltrating moisture. In addition to capturing soil moisture, plant roots absorb nutrients, minerals, and heavy metals, transporting them within the plant to the above-ground biomass. In this fashion, plant uptake affects the movement of radionuclides. The plant uptake model presented reflects rooting characteristics important to plant uptake, biomass turnover rates, and the ability of plants to uptake radionuclides from the soil. Parameters are provided for modeling plant uptake and estimating surface contaminant flux due to plant uptake under both current and potential future climate conditions with increased effective soil moisture. The term ''effective moisture'' is used throughout this report to indicate the soil moisture that is available to plants and is intended to be inclusive of all the variables that control soil moisture at a site (e.g., precipitation, temperature, soil texture, and soil chemistry). Effective moisture is a concept used to simplify a number of complex, interrelated soil processes for which there are too little data to model actual plant available moisture. The PA simulates both the flux of radionuclides across the land surface and the potential dose to humans from that flux. Surface flux is modeled here as the amount of soil contamination that is transferred from the soil by roots and incorporated into aboveground biomass. Movement of contaminants to the surface is the only transport mechanism evaluated with the model presented here

  11. Distribution of 3H-GABA uptake sites in the nematode Ascaris

    SciTech Connect

    Guastella, J.; Stretton, A.O. )

    1991-05-22

    The distribution of uptake sites for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the nematode Ascaris suum was examined by autoradiography of 3H-GABA uptake. Single neural processes in both the ventral and dorsal nerve cords were labeled with 3H-GABA. Serial section analysis identified the cells of origin of these processes as the RMEV-like and RMED-like neurons. These cells belong to a set of four neurons in the nerve ring, all of which are labeled by 3H-GABA. 3H-GABA labeling of at least two other sets of cephalic neurons was seen. One of these pairs consists of medium-sized lateral ganglia neurons, located at the level of the amphid commissure bundle. A second pair is located in the lateral ganglia at the level of the deirid commissure bundle. The position and size of these lateral ganglia cells suggest that they are the GABA-immunoreactive lateral ganglia cells frequently seen in whole-mount immunocytochemical preparations. Four neuronal cell bodies located in the retrovesicular ganglion were also labeled with 3H-GABA. These cells, which are probably cholinergic excitatory motor neurons, do not contain detectable GABA-like immunoreactivity. Heavy labeling of muscle cells was also observed. The ventral and dorsal nerve cord inhibitory motor neurons, which are known to contain GABA-like immunoreactivity, were not labeled above background with 3H-GABA. Together with the experiments reported previously, these results define three classes of GABA-associated neurons in Ascaris: (1) neurons that contain endogenous GABA and possess a GABA uptake system; (2) neurons that contain endogenous GABA, but that either lack a GABA uptake system or possess a GABA uptake system of low activity; (3) neurons that possess a GABA uptake system, but that lack endogenous GABA.

  12. Autoradiography of dopamine receptors and dopamine uptake sites in the spontaneously hypertensive rat

    SciTech Connect

    Kujirai, K.; Przedborski, S.; Kostic, V.; Jackson-Lewis, V.; Fahn, S.; Cadet, J.L. )

    1990-11-01

    We examined the status of dopamine (DA) D1 and D2 receptors by using (3H)SCH 23390 and (3H)spiperone binding, respectively, and DA uptake sites by using (3H)mazindol binding in spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. SHR showed significantly higher (3H)SCH 23390 and (3H)spiperone binding in the caudate-putamen (CPu), the nucleus accumbens (NAc) and the olfactory tubercle (OT) in comparison to the SD rats. There were no significant differences in (3H)mazindol-labeled DA uptake sites between the two strains. Unilateral 6-hydroxydopamine (6-OHDA) injection into the striatum resulted in more than 90% depletion of DA uptake sites in the CPu in both strains. 6-OHDA-induced DA depletion was associated with significant increases in striatal (3H)spiperone binding which were of similar magnitude in the SD rats (+64.1%) and SHR (+51.3%). There were only small decreases (-5.4%) in D1 receptor binding in the dorsolateral aspect of the CPu in the SHR, whereas there were no changes in striatal D1 receptors in the SD rats. These results indicate that, although the SHR have higher concentrations of both D1 and D2 receptors in the basal ganglia, these receptors are regulated in a fashion similar to DA receptors in SD rats after 6-OHDA-induced striatal DA depletion.

  13. Uptake of selected organics and metals by terrestrial vegetation and insects at a site in Arizona

    SciTech Connect

    Day, C.H.; Ayers, T.A.; Ellingson, S.B.; Braddy, L.

    1995-12-31

    As part of an investigation at a CERCLA site in Arizona, 27 potential sources of contamination (PSCS) were identified for study. A screening level ecological risk assessment was conducted for each PSC using generic plant uptake factors and conservative exposure parameters. Risk estimates were calculated for the indicator species using the hazard index (HI) approach. Results of the screening level assessment indicated that 4 of the 27 PSCs required further evaluation due to elevated HIs. The contaminants of potential concern (COPCS) are antimony, cadmium, lead, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and total petroleum hydrocarbons (TPH). A field sampling program at the 4 PSCs and a site-specific background location was conduct4ed to collect the food sources for the indicator species. The samples have been analyzed for the COPCs and the results are being used to validate the screening level risk calculations. The site-specific soil-to-plant uptake factors will be compared to generic soil-to-plant uptake factors obtained from the scientific literature, with emphasis placed on studies done in similar arid environments. Contaminant-specific soil-to-insect bioaccumulation factors (BAFs) will be presented and compared to BAFs derived using published bioaccumulation models.

  14. Calibration of a plant uptake model with plant- and site-specific data for uptake of chlorinated organic compounds into radish.

    PubMed

    Trapp, Stefan

    2015-01-01

    The uptake of organic pollutants by plants is an important process for the exposure of humans to toxic chemicals. The objective of this study was to calibrate the parameters of a common plant uptake model by comparison to experimental results from literature. Radish was grown in contaminated soil (maximum concentration 2.9 mg/kg dw) and control plot. Uptake of HCHs, HCB, PCBs, and DDT plus metabolites was studied (log K(ow) 3.66 to 7.18). Measured BCF roots-to-soil were near 1 g/g dw on the control plot and about factor 10 lower for the contaminated soil. With default data set, uptake into roots of most substances was under predicted up to factor 100. The use of site-specific data improved the predictions. Consideration of uptake from air into radish bulbs was relevant for PCBs. Measured BCF shoots ranged from <0.1 to >10 g/g dw and were much better predicted by the standard model. The results with default data and site-specific data were similar. Deposition from air was the major uptake mechanism into shoots. Transport from soil with resuspended particles was only relevant for the contaminated plot. The calculation results (in dry weight) were most sensitive to changes of the water content of plant tissue. PMID:25426767

  15. Uptake of selected organics and metals by terrestrial vegetation and insects at a site in Arizona

    SciTech Connect

    Day, C.H.; Ayers, T.A.

    1995-12-31

    As part of an investigation at a CERCLA site in Arizona, 27 potential sources of contamination (PSCs) were identified for study. A screening level ecological risk assessment was conducted for each PSC using generic plant uptake factors and conservative exposure parameters. Risk estimates were calculated for the indicator species using the hazard index (HI) approach. Results of the screening level risk assessment indicated that 4 of the 27 PSCs required further evaluation due to elevated HIs. The contaminants of potential concern (COPCs) are antimony, cadmium, lead, polycyclic aromatic hydrocarbons, PCBS, and total petroleum hydrocarbons. A field sampling program is underway to collect the food sources (i.e., terrestrial vegetation and ground-level herbivorous insects) for the indicator species. The samples will be analyzed for the COPCs and the results used to validate the screening level risk calculations. The site-specific soil-to-plant uptake factors will be compared to generic soil-to-plant uptake factors obtained from the scientific literature, with emphasis placed on studies done in similar arid environments. Contaminant-specific soil-to-insect bioaccumulation factors (BAFs) will be presented and compared with BAFs derived using published bioaccumulation models.

  16. Addition of the Neurokinin-1-Receptor Antagonist (RA) Aprepitant to a 5-Hydroxytryptamine-RA and Dexamethasone in the Prophylaxis of Nausea and Vomiting Due to Radiation Therapy With Concomitant Cisplatin

    SciTech Connect

    Jahn, Franziska; Jahn, Patrick; Sieker, Frank; Vordermark, Dirk; Jordan, Karin

    2015-08-01

    Purpose: To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy–induced nausea and vomiting. Patients and Methods: This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in this period. Results: Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03). Conclusion: This is the first study of an NK1-RA–containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.

  17. Coherence between woody carbon uptake and net ecosystem productivity at five eddy-covariance sites

    NASA Astrophysics Data System (ADS)

    Babst, F.; Bouriaud, O.; Papale, D.; Gielen, B.; Janssens, I.; Nikinmaa, E.; Ibrom, A.; Wu, J.; Bernhofer, C.; Koestner, B.; Gruenwald, T.; Seufert, G.; Ciais, P.; Frank, D. C.

    2013-12-01

    Forest growth ranks amongst the most important processes that determine the carbon balance of terrestrial ecosystems. Quantifications of forest carbon cycling can be made e.g. using biometric and eddy-covariance (EC) techniques. Both offer different perspectives on carbon uptake and attempts to combine them have been inconsistent and variably successful in the past. This contributes to persistent uncertainties regarding carbon allocation in forest ecosystems and complicates precise vegetation model parameterization. Aiming to reconcile assessments of carbon cycling from biometric and EC techniques, we measured radial tree growth and wood density at five long-term EC stations across Europe. The resulting records were used to calculate annual carbon uptake during above-ground wood formation and compared to monthly and seasonal CO2-flux measurements. Efforts were made to identify i) the time periods when EC and tree-ring data correspond best in different parts of Europe and ii) the fraction of eddy-fluxes which is associated with changes in above-ground woody carbon stocks. Biometric measurements and net ecosystem productivity (NEP) proved largely compatible at seasonal time scales while relationships with gross primary productivity (GPP) were often weaker. Results suggest a partitioning of sequestered carbon mainly used for volume increase (January-June) and a combination of cell-wall thickening and storage (July-September). The inter-annual variability in above-ground woody carbon uptake was significantly linked with absolute productivity ranging between 69-366 g C m-2 y-1 at boreal and temperate sites, thereby accounting for 10-25% of GPP, 15-32% of TER, and 25-80% of NEP. These findings from sites representing the major European climate zones and tree species contribute to improved quantification of above-ground carbon allocation in forests. Furthermore, they refine knowledge on processes driving ecosystem productivity important for e.g. vegetation models and

  18. Vanadium uptake and translocation in dominant plant species on an urban coastal brownfield site.

    PubMed

    Qian, Yu; Gallagher, Frank J; Feng, Huan; Wu, Meiyin; Zhu, Qingzhi

    2014-04-01

    This study, conducted at a brownfield site in New Jersey, USA, investigated factors controlling V uptake and translocation in naturally assembled plant species. Six dominant species were collected from 22 stations in the study area. We found that V concentration in the plants decreased in a sequence of root>leaf>stem. No significant differences were found among the six dominant plant species in terms of root V uptake efficiency (V BCF) and V root to shoot translocation (V TF). Although soil pH and TOC did not show significant impact on V accumulation in the roots, soil labile V content showed significant positive linear correlation (p<0.05) with plant root V. Non-linear regression analysis indicates that V translocation efficiency decreases with increasing concentration in the soil, implying that excessive V in the soil might inhibit its absorption by the plant roots. Leaf V concentration was constant in all the plant species regardless of the variation in soil V concentration. The study shows that the six dominant plant species on site had limited amount of V translocated to the aerial part of the plant. PMID:24518306

  19. Adding 5-hydroxytryptamine receptor type 3 antagonists may reduce drug-induced nausea in poor insight obsessive-compulsive patients taking off-label doses of selective serotonin reuptake inhibitors: a 52-week follow-up case report

    PubMed Central

    2010-01-01

    Poor-insight obsessive-compulsive disorder (PI-OCD) is a severe form of OCD where the 'typically obsessive' features of intrusive, 'egodystonic' feelings and thoughts are absent. PI-OCD is difficult to treat, often requiring very high doses of serotonergic drugs as well as antipsychotic augmentation. When this occurs, unpleasant side effects as nausea are common, eventually further reducing compliance to medication and increasing the need for pharmacological alternatives. We present the case of a PI-OCD patient who developed severe nausea after response to off-label doses of the selective serotonin reuptake inhibitor (SSRI), fluoxetine. Drug choices are discussed, providing pharmacodynamic rationales and hypotheses along with reports of rating scale scores, administered within a follow-up period of 52 weeks. A slight reduction of fluoxetine dose, augmentation with mirtazapine and a switch from amisulpride to olanzapine led to resolution of nausea while preserving the anti-OCD therapeutic effect. Mirtazapine and olanzapine have already been suggested for OCD treatment, although a lack of evidence exists about their role in the course of PI-OCD. Both mirtazapine and olanzapine also act as 5-hydroxytryptamine receptor type 3 (5-HT3) blockers, making them preferred choices especially in cases of drug-induced nausea. PMID:21143969

  20. Differential visualization of dopamine and norepinephrine uptake sites in rat brain using (/sup 3/H)mazindol autoradiography

    SciTech Connect

    Javitch, J.A.; Strittmatter, S.M.; Snyder, S.H.

    1985-06-01

    Mazindol is a potent inhibitor of neuronal dopamine (DA) and norepinephrine (NE) uptake. DA and NE uptake sites in rat brain have been differentially visualized using (/sup 3/H)mazindol autoradiography. At appropriate concentrations, desipramine (DMI) selectively inhibits (/sup 3/H)mazindol binding to NE uptake sites without significantly affecting binding to DA uptake sites. The localization of DMI-insensitive specific (/sup 3/H) mazindol binding, reflecting DA uptake sites, is densest in the caudate-putamen, the nucleus accumbens, the olfactory tubercle, the subthalamic nucleus, the ventral tegmental area, the substantia nigra (SN) pars compacta, and the anterior olfactory nuclei. In contrast, the localization of DMI-sensitive specific (/sup 3/H)mazindol binding, representing NE uptake sites, is densest in the locus coeruleus, the nucleus of the solitary tract, the bed nucleus of the stria terminalis, the paraventricular and periventricular nuclei of the hypothalamus, and the anteroventral thalamus. The distribution of DMI-insensitive specific (/sup 3/H)mazindol binding closely parallels that of dopaminergic terminal and somatodendritic regions, while the distribution of DMI-sensitive specific (/sup 3/H)mazindol binding correlates well with the regional localization of noradrenergic terminals and cell bodies. Injection of 6-hydroxydopamine, ibotenic acid, or colchicine into the SN decreases (/sup 3/H)mazindol binding to DA uptake sites in the ipsilateral caudate-putamen by 85%. In contrast, ibotenic acid lesions of the caudate-putamen do not reduce (/sup 3/H)mazindol binding to either the ipsilateral or contralateral caudate-putamen.

  1. Anatomic Site Variability in Rat Skeletal Uptake and Desorption Of Fluorescently Labeled Bisphosphonate

    PubMed Central

    Wen, D.; Qing, L.; Harrison, G.; Golub, E.; Akintoye, S.O.

    2010-01-01

    Objectives Bisphosphonates commonly used to treat osteoporosis, Paget’s disease, multiple myeloma, hypercalcemia of malignancy and osteolytic lesions of cancer metastasis have been associated with bisphosphonate-associated jaw osteonecrosis (BJON). The underlying pathogenesis of BJON is unclear, but disproportionate bisphosphonate concentration in the jaw has been proposed as one potential etiological factor. This study tested the hypothesis that skeletal biodistribution of intravenous bisphosphonate is anatomic site-dependent in a rat model system. Materials and Methods Fluorescently labeled pamidronate was injected intravenously in athymic rats of equal weights followed by in vivo whole body fluorimetry, ex vivo optical imaging of oral, axial and appendicular bones and ethylenediaminetetraacetic acid bone decalcification to assess hydroxyapatite-bound bisphosphonate. Results Bisphosphonate uptake and bisphosphonate released per unit calcium were similar in oral and appendicular bones but lower than those in axial bones. Hydroxyapatite-bound bisphosphonate liberated by sequential acid decalcification was highest in oral relative to axial and appendicular bones (p < 0.05). Conclusions This study demonstrates regional differences in uptake and release of bisphosphonate from oral, axial and appendicular bones of immune deficient rats. PMID:21122034

  2. Water uptake by two river red gum ( Eucalyptus camaldulensis) clones in a discharge site plantation in the Western Australian wheatbelt

    NASA Astrophysics Data System (ADS)

    Marshall, John K.; Morgan, Anne L.; Akilan, Kandia; Farrell, Richard C. C.; Bell, David T.

    1997-12-01

    The heat-pulse technique was used to estimate year-long water uptake in a discharge zone plantation of 9-year-old clonal Eucalyptus camaldulensis Dehnh. near Wubin, Western Australia. Water uptake matched rainfall closely during weter months but exceeded rainfall as the dry season progressed. Average annual water uptake (1148 mm) exceeded rainfall (432 mm) by about 2.7 fold and approached 56% of pan evaporation for the area. The data suggest that at least 37% (i.e. ( {1}/{2.7}) × 100 ) of the lower catchment discharge zone should be planted to prevent the rise of groundwater. Water uptake varied with soil environment, season and genotype. Upslope trees used more water than did downslope trees. Water uptake was higher in E. camaldulensis clone M80 than in clone M66 until late spring. The difference reversed as summer progressed. Both clones, however, have the potential to dry out the landscape when potential evapotranspiration exceeds rainfall. This variation in water uptake within the species indicates the potential for manipulating plantation uptake by matching tree characteristics to site characteristics. Controlled experiments on the heat-pulse technique indicated accuracy errors of approximately 10%. This, combined with the ability to obtain long-term, continuous data and the superior logistics of use of the heat-pulse technique, suggests that results obtained by it would be much more reliable than those achieved by the ventilated chamber technique.

  3. Oligomer size of the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor revealed by fluorescence correlation spectroscopy with photon counting histogram analysis: evidence for homodimers without monomers or tetramers.

    PubMed

    Herrick-Davis, Katharine; Grinde, Ellinor; Lindsley, Tara; Cowan, Ann; Mazurkiewicz, Joseph E

    2012-07-01

    Fluorescence correlation spectroscopy (FCS) and photon counting histogram (PCH) are techniques with single molecule sensitivity that are well suited for examining the biophysical properties of protein complexes in living cells. In the present study, FCS and PCH were applied to determine the diffusion coefficient and oligomeric size of G-protein-coupled receptors. FCS was used to record fluctuations in fluorescence intensity arising from fluorescence-tagged 5-hydroxytryptamine 2C (5-HT(2C)) receptors diffusing within the plasma membrane of HEK293 cells and rat hippocampal neurons. Autocorrelation analysis yielded diffusion coefficients ranging from 0.8 to 1.2 μm(2)/s for fluorescence-tagged receptors. Because the molecular brightness of a fluorescent protein is directly proportional to the number of fluorescent proteins traveling together within a protein complex, it can be used to determine the oligomeric size of the protein complex. FCS and PCH analysis of fluorescence-tagged 5-HT(2C) receptors provided molecular brightness values that were twice that of GFP and YFP monomeric controls, similar to a dimeric GFP control, and unaltered by 5-HT. Bimolecular fluorescence complementation of the N- and C-terminal halves of YFP attached to 5-HT(2C) receptors was observed in endoplasmic reticulum/Golgi and plasma membranes with a brightness equal to monomeric YFP. When GFP-tagged 5-HT(2C) receptors were co-expressed with a large excess of untagged, non-fluorescent 5-HT(2C) receptors, the molecular brightness was reduced by half. PCH analysis of the FCS data were best described by a one-component dimer model without monomers or tetramers. Therefore, it is concluded that 5-HT(2C) receptors freely diffusing within the plasma membrane are dimeric. PMID:22593582

  4. Sites of calcium uptake of fish otoliths correspond with macular regions rich of carbonic anhydrase

    NASA Astrophysics Data System (ADS)

    Beier, M.; Anken, R.; Hilbig, R.

    2006-01-01

    Based on pharmacological data, it has been suggested that the enzyme carbonic anhydrase (CAH) plays a prominent role in the mineralization of fish otoliths. To directly test this proposal, the topographical distribution of CAH was histochemically analyzed in the utricular and saccular maculae of larval cichlid fish Oreochromis mossambicus. Further investigations were focussed on the sites of otolithic calcium uptake using the fluorescent calcium tracer alizarin-complexone (AC). Both in the utricle and the saccule, CAH-reactivity was prominent in regions on both sides of the sensory macula (centrifugal (cf) and centripetal (cp) areas), which reportedly contain ionocytes, specialized cells regulating the ionic composition of the endolymph. (The terms centrifugal and centripetal were chosen instead of lateral and medial, because the saccule is positioned perpendicular to the utricle; “lateral” and “medial” thus do not allow an unambiguous allocation of the respective regions.) In the saccule, the size of cf and cp did not differ from each other, whereas, in the utricle, cp was considerably larger as compared to cf (CAH-reactivity per μm2 was nearly identical in both areas of both endorgans). AC-incubation resulted in a fluorescent band on the proximal surface of the otoliths (this surface lies next to the sensory epithelium). In saccular otoliths (sagittae), the area of the band did not differ between centrifugal and centripetal otolith regions, whereas in the utricular otoliths (lapilli), the area of the centripetal AC-band was larger in size as compared to the centrifugal one (AC-fluorescence per μm2 did not differ between the areas analyzed in both types of otoliths). These results strongly suggest that calcium/carbonate uptake of otoliths takes place especially in those regions of their proximal face which are located adjacent to CAH-rich areas of the macular epithelium. It is thus concluded that CAH is directly involved in otolith calcification. The

  5. Sites of Calcium Uptake of Fish Otoliths correspond with macular Regions rich of Carbonic Anhydrase

    NASA Astrophysics Data System (ADS)

    Beier, M.; Anken, R.; Hilbig, R.

    Based on pharmacological data, it has been suggested that the enzyme carbonic anhydrase (CA) plays a prominent role in the mineralization of fish otoliths. In order to directly test this proposal, the topographical distribution of CA was histochemically analyzed in the utricular and saccular maculae of larval cichlid fish Oreochromis mossambicus. Further investigations were focussed on the sites of otolithic calcium uptake using the fluorescent calcium tracer alizarin-complexone (AC). Both in the utricle and the saccule, CA-rich areas were located on both sides of the sensory macula which reportedly contain ionocytes, specialized cells regulating the ionic composition of the endolymph. The reactivity of CA per μm^2 was similar in all of these regions. In the saccule, the size of the dorsal and ventral CA-rich regions did not differ (and thus yielded the same total CA-reactivity), whereas, in the utricle, the medial CA-rich portion was considerably larger (and therefore had a higher total CA-reactivity) as compared to the laterally located area (the CA-rich regions are homologous in the both endorgans; however, anatomical references relative to the body axes of a fish differ, since the two maculae are located perpendicular to each other). AC-incubation resulted in a fluorescent band on the proximal surface of the otoliths (this surface lies next to the sensory epithelium). In saccular otoliths (sagittae), AC-fluorescence was distributed evenly within the band. However, in the utricular otoliths (lapilli), the medial portion of the AC-band was considerably broader as compared to its lateral aspect. These results strongly suggest that calcium uptake of otoliths takes place especially in those regions of their proximal face which are located adjacent to CA-rich areas of the macular epithelium. It is thus concluded that CA is directly involved in otolith calcification. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB

  6. Synthesis of pyridylallylamines related to zimelidine and their inhibition of neuronal monoamine uptake.

    PubMed

    Högberg, T; Ulff, B; Renyi, A L; Ross, S B

    1981-12-01

    Analogues of the antidepressant agent zimelidine [6, (Z)-3-(4-bromophenyl)-N,N-dimethyl-3-(3-pyridyl)allylamine], a selective inhibitor of neuronal 5-hydroxytryptamine reuptake, were synthesized by several routes with the aim of obtaining compounds having a cis configuration (with respect to pyridyl and allylamine). Two methods utilized suitably substituted benzoylpyridines as starting materials. In two other routes, the bromine in 6 was either directly displaced (CN) or converted via the corresponding lithio derivative to H, Cl, I, Me, SiMe3, and SMe. The configurations were determined by UV, 1H NMR, and lanthanide-induced shifts in 1H NMR. The compounds were evaluated as uptake inhibitors by measuring the accumulation of [3H]noradrenaline and 5-hydroxy[14C]tryptamine in mouse brain slices (in vitro and in vivo). Para substitution favored 5-hydroxytryptamine activity and ortho substitution favored NA activity in the cis series. The in vitro effect on 5-hydroxytryptamine was rather insensitive to variations in the para substituent, whereas pronounced effects in vivo were observed only with Cl, Br (6), and I. PMID:6458703

  7. Enhancing H[subscript 2] Uptake by 'Close-Packing' Alignment of Open Copper Sites in Metal-Organic Frameworks

    SciTech Connect

    Wang, Xi-Sen; Ma, Shengqian; Forster, Paul M.; Yuan, Daqiang; Eckert, Juergen; López, Joseph J.; Murphy, Brandon J.; Parise, John B.; Zhou, Hong-Cai

    2010-10-15

    Inspired by close-packing of spheres, to strengthen the framework-H{sub 2} interaction in MOFs (metal-organic frameworks), a strategy is devised to increase the number of nearest neighboring open metal sites ofe ach H{sub 2}-hosting cage, and to align the open metal sites toward the H{sub 2} molecules. Two MOF polymorphs were made, one exhibiting a record high hydrogen uptake of 3.0 wt% at 1 bar and 77 k.

  8. Effects of high-dose fenfluramine treatment on monoamine uptake sites in rat brain: Assessment using quantitative autoradiography

    SciTech Connect

    Appel, N.M.; Mitchell, W.M.; Contrera, J.F.; De Souza, E.B. )

    1990-01-01

    Fenfluramine is an amphetamine derivative that in humans is used primarily as an anorectic agent in the treatment of obesity. In rats, subchronic high-dose d,l-fenfluramine treatment (24 mg/kg subcutaneously, twice daily for 4 days) causes long-lasting decreases in brain serotonin (5HT), its metabolite 5-hydroxyindoleacetic acid, and high-affinity 5HT uptake sites. Moreover, this high-dose treatment regimen causes both selective long-lasting decreases in fine-caliber 5HT-immunoreactive axons and appearance of other 5HT-immunoreactive axons with morphology characteristic of degenerating axons. Determination of the potential neurotoxic effects of fenfluramine treatment using immunohistochemistry is limited from the perspectives that staining is difficult to quantify and that it relies on presence of the antigen (in this case 5HT), and the 5HT-depleting effects of fenfluramine are well known. In the present study, we used quantitative in vitro autoradiography to assess, in detail, the density and regional distribution of (3H)paroxetine-labeled 5HT and (3H)mazindol-labeled catecholamine uptake sites in response to the high-dose fenfluramine treatment described above. Because monoamine uptake sites are concentrated on monoamine-containing nerve terminals, decreases in uptake site density would provide a quantitative assessment of potential neurotoxicity resulting from this fenfluramine treatment regimen. Marked decreases in densities of (3H)paroxetine-labeled 5HT uptake sites occurred in brain regions in which fenfluramine treatment decreased the density of 5HT-like immunostaining when compared to saline-treated control rats. These included cerebral cortex, caudate putamen, hippocampus, thalamus, and medial hypothalamus.

  9. Similarity of nutrient uptake and root dimensions of Engelmann spruce and subalpine fir at two contrasting sites in Colorado

    SciTech Connect

    Yanai, R; McFarlane, K; Lucash, M; Kulpa, S; Wood, D

    2009-10-09

    Nutrient uptake capacity is an important parameter in modeling nutrient uptake by plants. Researchers commonly assume that uptake capacity measured for a species can be used across sites. We tested this assumption by measuring the nutrient uptake capacity of intact roots of Engelmann spruce (Picea engelmanni Parry) and subalpine fir (Abies lasiocarpa (Hook.) Nutt.) at Loch Vale Watershed and Fraser Experimental Forest in the Rocky Mountains of central Colorado. Roots still attached to the tree were exposed to one of three concentrations of nutrient solutions for time periods ranging from 1 to 96 hours, and solutions were analyzed for ammonium, nitrate, calcium, magnesium, and potassium. Surprisingly, the two species were indistinguishable in nutrient uptake within site for all nutrients (P > 0.25), but uptake rates differed by site. In general, nutrient uptake was higher at Fraser (P = 0.01, 0.15, 0.03, 0.18 for NH{sub 4}{sup +}, NO{sub 3}{sup -}, Ca{sup 2+}, and K{sup +}, respectively), which is west of the Continental Divide and has lower atmospheric deposition of N than Loch Vale. Mean uptake rates by site for ambient solution concentrations were 0.12 {micro}mol NH{sub 4}{sup +} g{sub fwt}{sup -1} h{sup -1}, 0.02 {micro}mol NO{sub 3}{sup -} g{sub fwt}{sup -1}, 0.21 {micro}mol Ca{sup 2+} g{sub fwt}{sup -1} h{sup -1}, and 0.01 {micro}mol Mg{sup 2+} g{sub fwt}{sup -1} h{sup -1} at Loch Vale, and 0.21 {micro}mol NH{sub 4}{sup +} f{sub fwt}{sup -1}h{sup -1}, 0.04 {micro}mol NO{sub 3}{sup -} g{sub fwt}{sup -1} h{sup -1}, 0.51 {micro}mol Ca{sup 2+}g{sub fwt}{sup -1}h{sup -1}, and 0.07 {micro}mol Mg{sup 2+} f{sub fwt}{sup -1}h{sup -1} at Fraser. The importance of site conditions in determining uptake capacity should not be overlooked when parameterizing nutrient uptake models. We also characterized the root morphology of these two species and compared them to other tree species we have measured at various sites in the northeastern USA. Engelman spruce and subalpine fir

  10. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with\\ increased motor disability.

    PubMed

    Iravani, Mahmoud M; Tayarani-Binazir, Kayhan; Chu, Wing B; Jackson, Michael J; Jenner, Peter

    2006-12-01

    5-Hydroxytryptamine 1a (5-HT(1a)) receptor agonists, such as sarizotan and tandospirone, are reported to reduce levodopa-induced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques and in Parkinson's disease without worsening motor disability. However, these compounds are not specific for 5-HT(1a) receptors and also possess dopamine antagonist actions. We now report on the effects of (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin [(R)-(+)-8-OHDPAT], a selective 5-HT(1a) agonist lacking dopaminergic activity, on motor disability and dyskinesia (chorea and dystonia) in levodopa-primed MPTP-treated common marmosets. Administration of (R)-(+)-8-OHDPAT (0.2, 0.6, and 2.0 mg/kg s.c), in conjunction with levodopa/carbidopa (12.5 mg/kg each p.o.) to levodopa-primed animals, dose-dependently reduced levodopa-induced chorea but did not affect dystonic movements. However, (R)-(+)-8-OHDPAT treatment also reduced locomotor activity and the reversal of motor disability. Administration of (R)-(+)-8-OHDPAT alone had no effects of motor behaviors. The effects of (R)-(+)-8-OHDPAT on levodopa-induced motor behaviors were antagonized by the 5-HT(1a) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate (WAY-100635) (1.0 mg/kg s.c.). Administration of (R)-(+)-8-OHDPAT (0.6 mg/kg s.c.) also reduced chorea produced by the administration of the D(2)/D(3) dopamine receptor agonist pramipexole (0.06 mg/kg p.o.) to levodopa-primed MPTP-treated animals. However, again the increase in locomotor activity and reversal of motor disability produced by pramipexole were also inhibited. These data suggest that selective 5-HT(1a) agonists do not provide an effective means of suppressing levodopa-induced dyskinesia, except with worsening of parkinsonism. PMID:16959959

  11. Influence of water uptake on the aerosol particle light scattering at remote sites (Invited)

    NASA Astrophysics Data System (ADS)

    Zieger, P.; Fierz-Schmidhauser, R.; Baltensperger, U.; Weingartner, E.

    2013-12-01

    Since ambient aerosol particles experience hygroscopic growth at enhanced relative humidity (RH), their microphysical and optical properties - especially the aerosol light scattering - are also strongly dependent on RH. The knowledge of this RH effect is of importance for climate forcing calculations or for the comparison of remote sensing with in-situ measurements because in the field aerosol in-situ measurements are often performed under dry conditions. The scattering enhancement factor f(RH,λ) is the key parameter to describe this effect of water uptake on the particle light scattering. It is defined as the particle light scattering coefficient σ(RH) at a certain RH and wavelength λ divided by its dry value. Here, we will present results from two remote sites: the Jungfraujoch located at 3580 m a.s.l. in the Swiss Alps and from Zeppelin station located at 78.5°N in the Arctic (Fierz-Schmidhauser et al., 2010; Zieger et al., 2010). Various aerosol optical and microphysical parameters were recorded at these sites using in-situ and remote sensing techniques. The scattering enhancement varied largely from very low values of f(RH=85%,λ=550 nm) around 1.28 for mineral dust transported to the Jungfraujoch to 3.41 for pristine Arctic aerosol. Compensating effects of size and hygroscopicity were observed in the Arctic, i.e. small but less hygroscopic particles eventually had the same magnitude in f(RH) as large but more hygroscopic particles like sea salt. Closure studies and Mie simulations showed that both size and chemical composition determine the magnitude of f(RH). The f(RH)-values from the two remote sites will also be related to values measured at other maritime, rural, and continental sites in Europe (Zieger et al., 2013). Active and passive remote sensing techniques were used to study the vertical distribution of aerosol optical properties around Jungfraujoch. Part of these in-situ measured parameters, together with the RH-dependent σ(RH) were used to

  12. Modeling the dynamic root water uptake and its hydrological impact at the Reserva Jaru site in Amazonia

    NASA Astrophysics Data System (ADS)

    Zheng, Zhe; Wang, Guiling

    2007-12-01

    An empirical approach is proposed to represent the impact of dynamic root water uptake by plant roots in two land surface models (Community Land Model version 3 (CLM3) and Integrated Biosphere Simulator version 2 (IBIS2)). This approach is compared with a more physically based approach that simulates the hydraulic redistribution, using the Reserva Jaru site in Amazonia as an example. For each model and each approach, two different root profiles are experimented on, an exponential profile and an observed, deeper profile. In both CLM3 and IBIS2, including dynamic root uptake significantly improves the model simulation of latent heat fluxes, regardless of what root profile is used. In both models, the impact of hydraulic redistribution (as accounted for by the physically based approach) is comparable to that of a low degree of dynamic root water uptake (as accounted for by the empirical approach). The latent heat flux simulation in IBIS2 is closer to observation than is that in CLM3, with or without the impact of dynamic root water uptake. Despite the model improvement due to including dynamic root water uptake, significant biases in soil moisture simulations remain. Assimilating soil moisture observations into the land surface models produces a remarkably improved latent heat flux simulation. Parameterization in surface and subsurface runoff (which influences soil moisture) is suggested as a likely cause for the severe biases in the default model simulations, which highlights the critical importance of correctly simulating the fundamental hydrological processes in land surface models.

  13. 99mTC-Methylene diphosphonate uptake at injury site correlates with osteoblast differentiation and mineralization during bone healing in mice

    PubMed Central

    Zhong, Zhendong A; Peck, Anderson; Li, Shihong; VanOss, Jeff; Snider, John; Droscha, Casey J; Chang, Tingtung A; Williams, Bart O

    2015-01-01

    99mTc-Methylene diphosphonate (99mTc-MDP) is widely used in clinical settings to detect bone abnormalities. However, the mechanism of 99mTc-MDP uptake in bone is not well elucidated. In this study, we utilized a mouse tibia injury model, single-photon emission computed tomography (gamma scintigraphy or SPECT), ex vivo micro-computed tomography, and histology to monitor 99mTc-MDP uptake in injury sites during skeletal healing. In an ex vivo culture system, calvarial cells were differentiated into osteoblasts with osteogenic medium, pulsed with 99mTc-MDP at different time points, and quantitated for 99mTc-MDP uptake with a gamma counter. We demonstrated that 99mTc-MDP uptake in the injury sites corresponded to osteoblast generation in those sites throughout the healing process. The 99mTc-MDP uptake within the injury sites peaked on day 7 post-injury, while the injury sites were occupied by mature osteoblasts also starting from day 7. 99mTc-MDP uptake started to decrease 14 days post-surgery, when we observed the highest level of bony tissue in the injury sites. We also found that 99mTc-MDP uptake was associated with osteoblast maturation and mineralization in vitro. This study provides direct and biological evidence for 99mTc-MDP uptake in osteoblasts during bone healing in vivo and in vitro. PMID:26273540

  14. High and Reversible Ammonia Uptake in Mesoporous Azolate Metal-Organic Frameworks with Open Mn, Co, and Ni Sites.

    PubMed

    Rieth, Adam J; Tulchinsky, Yuri; Dincă, Mircea

    2016-08-01

    A series of new mesoporous metal-organic frameworks (MOFs) made from extended bisbenzenetriazolate linkers exhibit coordinatively unsaturated metal sites that are responsible for high and reversible uptake of ammonia. Isostructural Mn, Co, and Ni materials adsorb 15.47, 12.00, and 12.02 mmol of NH3/g, respectively, at STP. Importantly, these near-record capacities are reversible for at least three cycles. These results demonstrate that azolate MOFs are sufficiently thermally and chemically stable to find uses in recyclable sorption, storage, and potentially separation of chemically challenging and/or corrosive gases, especially when designed to exhibit a high density of open metal sites. PMID:27420652

  15. Cellular Uptake and Cytotoxicity of Drug-Peptide Conjugates Regulated by Conjugation Site

    PubMed Central

    Zhang, Pengcheng; Cheetham, Andrew G.; Lock, Lye Lin; Cui, Honggang

    2013-01-01

    Conjugation of anticancer drugs to hydrophilic peptides such as Tat is a widely adopted strategy to improve the drug’s solubility, cellular uptake and potency against cancerous cells. Here we report that attachment of an anticancer drug doxorubicin to the N- or C-terminal of the Tat peptide can have a significant impact on their cellular uptake, cytotoxicity against both drug-sensitive and drug-resistant cancer cells. We observed higher cellular uptake by both cell lines for C-terminal conjugate relative to the N-terminal analogue. Our results reveal that the C-terminal conjugate partially overcame the multi-drug resistance of cervical cancer cells, while the N-terminal conjugate showed no significant improvement in cytotoxicity when compared with free doxorubicin. We also found that both N- and C- conjugates offers a mechanism to circumvent drug efflux associated with multidrug resistance. PMID:23514455

  16. Prostacyclin biosynthesis and reduced 5-HT uptake after complement-induced endothelial injury in the dog isolated lung.

    PubMed Central

    Bult, H.; Heiremans, J. J.; Herman, A. G.; Malcorps, C. M.; Peeters, F. A.

    1988-01-01

    1. Pulmonary prostacyclin (PGI2) biosynthesis was evaluated in relation to endothelial integrity before and after complement activation in isolated plasma-perfused lung lobes of the dog. 2. The plasma was activated with zymosan (ZAP, n = 4), yeast cells (YAP, n = 4) or yeast with 3 microM indomethacin (Indo + YAP, n = 3). Immunoreactive 6-oxo-prostaglandin F1 alpha (i-6-oxo-PGF1 alpha) and thromboxane B2 (iTXB2) were measured to monitor PGI2 and TXA2 biosynthesis. 3. The kinetic parameters Km and Vmax of 5-hydroxytryptamine (5-HT) uptake were calculated on the basis of multiple indicator diffusion data to evaluate endothelial integrity. 4. YAP and ZAP induced a biphasic increase of the arterial perfusion pressure. The immediate pressure peak was partly mediated by TXA2 and the TXB2 was subsequently cleared by the lung. 5. The apparent Vmax of 5-HT uptake remained constant throughout the experiment. Thus, complement activation did not affect the number of endothelial 5-HT carrier sites available to the perfusate. 6. The apparent Km of 5-HT uptake was enhanced in 9 lungs exposed to activated plasma complement for 20 min. This decreased affinity for 5-HT probably reflects endothelial injury. It was transient as the apparent Km had returned to the baseline value after 60 min. 7. PGI2 clearance and biosynthesis were virtually absent in the control period. PGI2 formation increased drastically after infusion of ZAP or YAP and was proportional to the endothelial injury expressed as elevated Km or pulmonary oedema. Thus, PGI2 biosynthesis might be a marker of severe endothelial distress. PMID:3291998

  17. Different components of /sup 3/H-imipramine binding in rat brain membranes: relation to serotonin uptake sites

    SciTech Connect

    Gobbi, M.; Taddei, C.; Mennini, T.

    1988-01-01

    In the present paper, the authors confirm and extend previous studies showing heterogeneous /sup 3/H-imipramine (/sup 3/H-IMI) binding sites. Inhibition curves of various drugs (serotonin, imipramine, desmethyl-imipramine, d-fenfluramine, d-norfenfluramine and indalpine, a potent serotonin uptake inhibitor) obtained using 2 nM /sup 3/H-IMI and in presence of 120 mM NaCl, confirmed the presence of at least three /sup 3/H-IMI binding sites: two of these were serotonin-insensitive while the third one was selectively inhibited by serotonin and indalpine with nanomolar affinities. Moreover this last component was found to be selectively modulated by chronic imipramine treatment thus suggesting a close relation to serontonin uptake mechanism. These data indicate that the use of a more selective inhibitors of the serotonin-sensitive component (like indalpine or serotonin itself) to define non specific /sup 3/H-IMI, may be of help in understanding its relation with serotonin uptake system. 22 references, 2 figures, 2 tables.

  18. Knowledge, attitude, and uptake related to human papillomavirus vaccination among young women in Germany recruited via a social media site

    PubMed Central

    Remschmidt, Cornelius; Walter, Dietmar; Schmich, Patrick; Wetzstein, Matthias; Deleré, Yvonne; Wichmann, Ole

    2014-01-01

    Background: Many industrialized countries have introduced human papillomavirus (HPV) vaccination of young women, but vaccine uptake often remains suboptimal. This study aimed to investigate whether a social media site like Facebook is an appropriate tool to assess knowledge, attitude and uptake related to HPV vaccination in young women in Germany. Methods: Between December 2012 and January 2013 two different targeting strategies were implemented on Facebook, providing a link to an online questionnaire. Advertisements were displayed to female Facebook users aged 18–25 years living in Germany. During the simple targeting strategy, advertisements comprised health-related images along with various short titles and text messages. During the focused strategy, advertisements were targeted to users who in addition had certain fashion brands or pop stars listed on their profiles. The targeting strategies were compared with respect to participant characteristics. Univariate and multivariate analyses were used to identify factors associated with HPV vaccine uptake. Results: A total of 1161 women participated. The two targeting strategies resulted in significant differences regarding educational status and migrant background. Overall, awareness of HPV was high, but only 53% received at least one vaccine dose. In multivariate analysis, HPV vaccine uptake was independently associated with a physician's recommendation and trust in vaccine effectiveness. Concerns of adverse effects were negatively associated with vaccine uptake. Discussion: Social network recruitment permits fast and convenient access to young people. Sample characteristics can be manipulated by adjusting targeting strategies. There is further need for promoting knowledge of HPV vaccination among young women. Physicians have a major role in the vaccination decision-making process of young women. PMID:25483492

  19. Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modeling.

    PubMed

    Hirst, Warren D; Abrahamsen, Bjarke; Blaney, Frank E; Calver, Andrew R; Aloj, Lucia; Price, Gary W; Medhurst, Andrew D

    2003-12-01

    There is increasing evidence for a role of 5-hydroxytrypta-mine-6 (5-HT6) receptors in cognitive function. In the rat and human brain, 5-HT6 receptors are widely expressed and highly enriched in the basal ganglia. However, in the mouse brain, only very low levels of 5-HT6 receptor mRNA and receptor protein, measured by TaqMan reverse transcriptase-polymerase chain reaction and selective radioligand binding, could be detected, with no evidence of enrichment in the basal ganglia. The mouse receptor was cloned and transiently expressed in human embryonic kidney 293 cells to characterize its pharmacological profile. Despite significant sequence homology between human, rat, and mouse 5-HT6 receptors, the pharmacological profile of the mouse receptor was significantly different from the rat and human receptors. Four amino acid residues, conserved in rat and human and divergent in mouse receptors, were identified, and various mutant receptors were generated and their pharmacologies studied. Residues 188 (tyrosine in mouse, phenylalanine in rat and human) in transmembrane region 5 and 290 (serine in mouse, asparagine in rat and human) in transmembrane region 6 were identified as key amino acids responsible for the different pharmacological profiles. Molecular modeling of the receptor and docking of selective and nonselective compounds was undertaken to elucidate the ligand receptor interactions. The binding pocket was predicted to be different in the mouse compared with rat and human 5-HT6 receptors, and the models were in excellent agreement with the observed mutation results and have been used extensively in the design of further selective 5-HT6 antagonists. PMID:14645659

  20. Uptake and recycling of lead by boreal forest plants: Quantitative estimates from a site in northern Sweden

    NASA Astrophysics Data System (ADS)

    Klaminder, Jonatan; Bindler, Richard; Emteryd, Ove; Renberg, Ingemar

    2005-05-01

    As a consequence of deposition of atmospheric pollution, the lead concentration in the mor layer (the organic horizon) of remote boreal forest soils in Sweden is raised far above natural levels. How the mor will respond to decreased atmospheric pollution is not well known and is dependent on future deposition rates, downward migration losses and upward fluxes in the soil profile. Plants may contribute to the upward flux of lead by 'pumping' lead back to the mor surface through root uptake and subsequent litter fall. We use lead concentration and stable isotope ( 206Pb, 207Pb and 208Pb) measurements of forest vegetation to quantify plant uptake rates from the soil and direct from the atmosphere at two sites in northern Sweden; an undisturbed mature forest and a disturbed site with Scots pine ( Pinus sylvestris) growing on a recently exposed mineral soil (C-horizon) containing a minimum of atmospherically derived pollution lead. Analyses of forest mosses from a herbarium collection (spanning the last ˜100 yr) and soil matrix samples suggest that the atmospheric lead deposited on plants and soil has an average 206Pb/ 207Pb ratio of 1.15, while lead derived from local soil minerals has an average ratio of ˜1.47. Since the biomass of trees and field layer shrubs has an average 206Pb/ 207Pb ratio of ˜1.25, this indicates that 70% ± 10% of the inventory of 1 ± 0.8 mg Pb m -2 stored in plants in the mature forest originates from pollution. Needles, bark and apical stemwood of the pine growing on the disturbed soil, show lower 206Pb/ 207Pb ratios (as low as 1.21) than the roots and basal stemwood (having ratios > 1.36), which indicate that plants are able to incorporate lead directly from the atmosphere (˜50% of the total tree uptake). By partitioning the total uptake of lead into uptake from the atmosphere and different soil layers using an isotopic mixing model, we estimate that ˜0.03 ± 0.01, 0.02 ± 0.01 and 0.05 ± 0.01 mg Pb m -2 yr -1 (mean ± SD), is taken up

  1. Plant selective uptake of halogenated flame retardants at an e-waste recycling site in southern China.

    PubMed

    Wang, Shaorui; Wang, Yan; Luo, Chunling; Li, Jun; Yin, Hua; Zhang, Gan

    2016-07-01

    The concentrations and homolog patterns of halogenated flame retardants (HFRs) in vegetables grown at an e-waste contaminated site were investigated. Polybrominated diphenyl ethers (PBDEs) were the dominant HFRs in vegetable tissues, with concentrations ranging from 10.3 to 164 ng g(-1) and 1.16-107 ng g(-1) in shoots and roots, respectively, followed by novel brominated flame retardants (NBFRs) and dechlorane plus (DPs). This is an indication that PBDE contamination in vegetables grown around e-waste recycling sites may pose a risk to the local terrestrial ecosystem and residents. In addition, this is the first report on the concentrations and compositions of NBFRs in vegetables around e-waste recycling sites. The HFRs concentrations in vegetables varied greatly with the vegetable species, with the highest concentrations observed in Brassica oleracea var. capitata. Root concentration factors (RCF) decreased with increasing log Kow of HFRs, which indicated that the uptake of HFRs was controlled mainly by log Kow. Dissimilar HFRs profiles in shoots and roots suggested that the uptake and translocation of HFRs by plants were selective, with lower halogenated congeners prone to accumulation in vegetable tissues. Positive relationships between PBDEs and their substitutes were observed in vegetable tissues, suggesting that the replacement of PBDEs by NBFRs has not resulted in an obvious transition in plants within the study area. PMID:27149147

  2. Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4-Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity

    PubMed Central

    Strand, Joanna; Nordeman, Patrik; Honarvar, Hadis; Altai, Mohamed; Orlova, Anna; Larhed, Mats; Tolmachev, Vladimir

    2015-01-01

    Affibody molecules are small scaffold-based affinity proteins with promising properties as probes for radionuclide-based molecular imaging. However, a high reabsorption of radiolabeled Affibody molecules in kidneys is an issue. We have shown that the use of 125I-3-iodo-((4-hydroxyphenyl)ethyl)maleimide (IHPEM) for site-specific labeling of cysteine-containing Affibody molecules provides high tumor uptake but low radioactivity retention in kidneys. We hypothesized that the use of 4-iodophenethylmaleimide (IPEM) would further reduce renal retention of radioactivity because of higher lipophilicity of radiometabolites. An anti-human epidermal growth factor receptor type 2 (HER2) Affibody molecule (ZHER2:2395) was labeled using 125I-IPEM with an overall yield of 45±3 %. 125I-IPEM-ZHER2:2395 bound specifically to HER2-expressing human ovarian carcinoma cells (SKOV-3 cell line). In NMRI mice, the renal uptake of 125I-IPEM-ZHER2:2395 (24±2 and 5.7±0.3 % IA g−1at 1 and 4 h after injection, respectively) was significantly lower than uptake of 125I-IHPEM-ZHER2:2395 (50±8 and 12±2 % IA g−1at 1 and 4 h after injection, respectively). In conclusion, the use of a more lipophilic linker for the radioiodination of Affibody molecules reduces renal radioactivity. PMID:25969816

  3. Cellular sites of estrogen and antiestrogen uptake, retention and action: comparative autoradiographic studies in the immature rat uterus

    SciTech Connect

    Ennis, B.W.

    1987-01-01

    This purpose of this study is to clarify the mechanism of action of antiestrogens: agents used for treating breast cancer and as probes for studying the mechanisms of action of estrogen. Nuclear uptake and retention of estrogen and antiestrogen were determined in the different cell types of the immature rat uterus, by quantitative autoradiography, after an injection of tritiated hydroxytamoxifen ((/sup 3/H)TAM(OH)) or tritiated estradiol ((/sup 3/H)E/sub 2/). The effect of TAM(OH) and E/sub 2/ on progesterone receptor content was assessed in the different cell types by determining nuclear uptake of the synthetic progestin (/sup 3/H)Org 2058. The results indicate that antiestrogen and estrogen localize to nuclei of the same uterine cell types, but that this nuclear uptake differs among the uterine tissue compartments, that antiestrogen is taken up considerably slower and retained longer than estrogen and that antiestrogen and estrogen differentially affect progesterone receptor content in the different cell types. The results further suggest that antiestrogen-specific binding sites exist in the cytoplasm of uterine luminal epithelium.

  4. Selective labeling of serotonin uptake sites in rat brain by (/sup 3/H)citalopram contrasted to labeling of multiple sites by (/sup 3/H)imipramine

    SciTech Connect

    D'Amato, R.J.; Largent, B.L.; Snowman, A.M.; Snyder, S.H.

    1987-07-01

    Citalopram is a potent and selective inhibitor of neuronal serotonin uptake. In rat brain membranes (/sup 3/H)citalopram demonstrates saturable and reversible binding with a KD of 0.8 nM and a maximal number of binding sites (Bmax) of 570 fmol/mg of protein. The drug specificity for (/sup 3/H)citalopram binding and synaptosomal serotonin uptake are closely correlated. Inhibition of (/sup 3/H)citalopram binding by both serotonin and imipramine is consistent with a competitive interaction in both equilibrium and kinetic analyses. The autoradiographic pattern of (/sup 3/H)citalopram binding sites closely resembles the distribution of serotonin. By contrast, detailed equilibrium-saturation analysis of (/sup 3/H)imipramine binding reveals two binding components, i.e., high affinity (KD = 9 nM, Bmax = 420 fmol/mg of protein) and low affinity (KD = 553 nM, Bmax = 8560 fmol/mg of protein) sites. Specific (/sup 3/H)imipramine binding, defined as the binding inhibited by 100 microM desipramine, is displaced only partially by serotonin. Various studies reveal that the serotonin-sensitive portion of binding corresponds to the high affinity sites of (/sup 3/H)imipramine binding whereas the serotonin-insensitive binding corresponds to the low affinity sites. Lesioning of serotonin neurons with p-chloroamphetamine causes a large decrease in (/sup 3/H)citalopram and serotonin-sensitive (/sup 3/H)imipramine binding with only a small effect on serotonin-insensitive (/sup 3/H)imipramine binding. The dissociation rate of (/sup 3/H)imipramine or (/sup 3/H)citalopram is not altered by citalopram, imipramine or serotonin up to concentrations of 10 microM. The regional distribution of serotonin sensitive (/sup 3/H)imipramine high affinity binding sites closely resembles that of (/sup 3/H)citalopram binding.

  5. A comparison of 90Sr and 137Cs uptake in plants via three pathways at two Chernobyl-contaminated sites.

    PubMed

    Malek, M A; Hinton, T G; Webb, S B

    2002-01-01

    Foliar absorption of resuspended 90Sr, root uptake and contamination adhering to leaf surfaces (i.e. soil loading) were compared at two Chernobyl-contaminated sites, Chistogalovka and Polesskoye. Although foliar absorption of resuspended 90Sr was quantifiable, its contribution amounted to less than 10% of the plants' total, above-ground contamination. Root uptake was 200 times greater than foliar absorption at the near-field site of Chistogalovka and eight times greater at Polesskoye, where the fallout consisted of the more soluble condensation-type, rather than fuel particles. Strontium's bioavailability exceeded that of 137Cs (analyzed in the same plants) by orders of magnitude when compared using concentration ratios. Simplistic, cumulative effective dose calculations for humans ingesting 90Sr- and 137Cs-contaminated plants revealed that the dose at Chistogalovka was greater from 90Sr (185 mSv vs. 3 mSv from 137Cs), while at Polesskoye the dose from 137Cs (66 mSv) was 30 times greater than from 90Sr (2 mSv). PMID:11814162

  6. The cell pole: the site of cross talk between the DNA uptake and genetic recombination machinery.

    PubMed

    Kidane, Dawit; Ayora, Silvia; Sweasy, Joann B; Graumann, Peter L; Alonso, Juan C

    2012-01-01

    Natural transformation is a programmed mechanism characterized by binding of free double-stranded (ds) DNA from the environment to the cell pole in rod-shaped bacteria. In Bacillus subtilis some competence proteins, which process the dsDNA and translocate single-stranded (ss) DNA into the cytosol, recruit a set of recombination proteins mainly to one of the cell poles. A subset of single-stranded binding proteins, working as "guardians", protects ssDNA from degradation and limit the RecA recombinase loading. Then, the "mediators" overcome the inhibitory role of guardians, and recruit RecA onto ssDNA. A RecA·ssDNA filament searches for homology on the chromosome and, in a process that is controlled by "modulators", catalyzes strand invasion with the generation of a displacement loop (D-loop). A D-loop resolvase or "resolver" cleaves this intermediate, limited DNA replication restores missing information and a DNA ligase seals the DNA ends. However, if any step fails, the "rescuers" will repair the broken end to rescue chromosomal transformation. If the ssDNA does not share homology with resident DNA, but it contains information for autonomous replication, guardian and mediator proteins catalyze plasmid establishment after inhibition of RecA. DNA replication and ligation reconstitute the molecule (plasmid transformation). In this review, the interacting network that leads to a cross talk between proteins of the uptake and genetic recombination machinery will be placed into prospective. PMID:23046409

  7. Arsenic and lead uptake by Brassicas grown on an old orchard site.

    PubMed

    Lim, Maya P; McBride, Murray B

    2015-12-15

    Arugula (Eruca sativa) and collards (Brassica oleracea var. acephala), were grown at a former orchard where soils had been variably contaminated by lead arsenate pesticides. To test for the effect of compost on As and Pb transfer into plants, compost was added (0, 5, and 10% DW) to five plots representing a wide range of soil Pb and As. Arugula accumulated about 5 times higher As concentrations in above-ground tissues than collards, with high variability in individual plant concentrations. Soil to arugula transfer (uptake) coefficients were higher for As than for Pb, and increased with soil As. Crop concentrations of Pb varied widely within replicate samples of both arugula and collards. Arugula contamination by Pb was significantly correlated to soil total Pb, but collard contamination was not. Evidence was found using Al as an indicator of soil particle contamination of plant tissues that Pb in arugula was primarily due to soil particle deposition on foliar surfaces. Compost amendments reduced 0.01 M CaCl2 -extractable Pb but increased extractable As in the orchard soils. However, compost had the beneficial effect of reducing both As and Pb concentrations in harvested arugula grown on most of the plots. PMID:26280370

  8. Beta-test Results for an HPV Information Web site: GoHealthyGirls.org – Increasing HPV Vaccine Uptake in the United States

    PubMed Central

    Nodulman, Jessica A.; Kong, Alberta S.; Wheeler, Cosette M.; Buller, David B.; Woodall, W. Gill

    2014-01-01

    A web site, GoHealthyGirls, was developed to educate and inform parents and their adolescent daughters about human papillomavirus (HPV) and HPV vaccines. This article provides an overview of web site development and content followed by the results of a beta-test of the web site. 63 New Mexican parents of adolescent girls tested the site. Results indicated that GoHealthyGirls was a functioning and appealing web site. During this brief educational intervention, findings suggest that the web site has the potential to increase HPV vaccine uptake. This research supports the Internet as a valuable channel to disseminate health education and information to diverse populations. PMID:25221442

  9. Catecholamine uptake sites: characterization, localization, and a role in the production of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism

    SciTech Connect

    Javitch, J.A.

    1985-01-01

    Dopamine and norepinephrine are inactivated by specific high affinity transport systems which mediate the recapture of the amines into presynaptic nerve terminals. (/sup 3/H)Maxindol labels neuronal dopamine uptake sites in corpus striatum membranes and neuronal norepinephrine uptake sites in cerebral cortex and submaxillary/sublingual gland membranes. The potencies of various inhibitors of biogenic amine uptake in reducing (/sup 3/H)mazindol binding in striatal membranes correlate with their potencies for inhibition of neurona (/sup 3/H)dopamine accumulation, whereas their potencies in reducing (/sup 3/H)mazindol binding to cortical and salivary gland membranes correlate with their potencies for inhibition of neuronal (/sup 3/H)norepinephrine accumulation. The association of (/sup 3/H)mazindol binding sites with neuronal dopamine uptake sites in the corpus striatum is further supported by the reduction of (/sup 3/H)mazindol binding sites in striatal membranes following destruction of dopaminergic neurons by 6-hydroxydopamine. Similarly, destruction of noradrenergic neurons by N-(2-chloro-ethyl)-N-ethyl-2-bromobenzylamine(DSP-4) decreases (/sup 3/H)mazindol binding to cortical membranes. Dopamine and norepinephrine uptake sites in rat brain have been differentially visualized using (/sup 3/H)mazindol autoradiography. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathologic and clinical abnormalities in humans and animals that closely resemble idiopathic Parkinson disease. (/sup 3/H)MPTP binds with high affinity to brain membranes. The chemical specificity of the binding sites corresponds to structure-activity requirements for neurotoxicity.

  10. Metal uptake by homegrown vegetables - the relative importance in human health risk assessments at contaminated sites.

    PubMed

    Augustsson, Anna L M; Uddh-Söderberg, Terese E; Hogmalm, K Johan; Filipsson, Monika E M

    2015-04-01

    Risk assessments of contaminated land often involve the use of generic bioconcentration factors (BCFs), which express contaminant concentrations in edible plant parts as a function of the concentration in soil, in order to assess the risks associated with consumption of homegrown vegetables. This study aimed to quantify variability in BCFs and evaluate the implications of this variability for human exposure assessments, focusing on cadmium (Cd) and lead (Pb) in lettuce and potatoes sampled around 22 contaminated glassworks sites. In addition, risks associated with measured Cd and Pb concentrations in soil and vegetable samples were characterized and a probabilistic exposure assessment was conducted to estimate the likelihood of local residents exceeding tolerable daily intakes. The results show that concentrations in vegetables were only moderately elevated despite high concentrations in soil, and most samples complied with applicable foodstuff legislation. Still, the daily intake of Cd (but not Pb) was assessed to exceed toxicological thresholds for about a fifth of the study population. Bioconcentration factors were found to vary more than indicated by previous studies, but decreasing BCFs with increasing metal concentrations in the soil can explain why the calculated exposure is only moderately affected by the choice of BCF value when generic soil guideline values are exceeded and the risk may be unacceptable. PMID:25723126

  11. Comparison of the autoradiographic binding distribution of [3H]-gabapentin with excitatory amino acid receptor and amino acid uptake site distributions in rat brain.

    PubMed Central

    Thurlow, R. J.; Hill, D. R.; Woodruff, G. N.

    1996-01-01

    1. Gabapentin is a novel anticonvulsant with an unknown mechanism of action. Recent homogenate binding studies with [3H]-gabapentin have suggested a structure-activity relationship similar to that shown for the amino acid transport system responsible for the uptake of large neutral amino acids (LNAA). 2. The autoradiographic binding distribution of [3H]-gabapentin in rat brain was compared with the distributions for excitatory amino acid receptor subtypes and the uptake sites for excitatory and large neutral amino acids in consecutive rat brain sections. 3. Densitometric measurement of the autoradiographic images followed by normalisation with respect to the hippocampus CA1 stratum radiatum, was carried out before comparison of each binding distribution with that of [3H]-gabapentin by linear regression analysis. The correlation coefficients observed showed no absolute correlation was observed between the binding distributions of [3H]-gabapentin and those of the excitatory amino acid receptor subtypes. The acidic and large neutral amino acid uptake site distributions demonstrated a much closer correlation to the [3H]-gabapentin binding site distribution. The correlation coefficients for D-[3H]-aspartate, L-[3H]-leucine and L-[3H]-isoleucine binding site distributions were 0.76, 0.90 and 0.88 respectively. 4. Concentration-dependent inhibition by unlabelled gabapentin of autoradiographic binding of L-[3H]-leucine and L-[3H]-isoleucine was observed, with non-specific binding levels being reached at concentrations between 10 and 100 microM. 5. Excitotoxic quinolinic acid lesion studies in rat brain caudate putamen and autoradiography were carried out for the amino acid uptake sites mentioned above. The resulting glial infiltration of the lesioned areas was visualized by autoradiography using the peripheral benzodiazepine receptor specific ligand [3H]-PK11195. A significant decrease in binding density in the lesioned area compared with sham-operated animals was observed

  12. Metal uptake by homegrown vegetables – The relative importance in human health risk assessments at contaminated sites

    SciTech Connect

    Augustsson, Anna L.M.; Uddh-Söderberg, Terese E.; Hogmalm, K. Johan; Filipsson, Monika E.M.

    2015-04-15

    Risk assessments of contaminated land often involve the use of generic bioconcentration factors (BCFs), which express contaminant concentrations in edible plant parts as a function of the concentration in soil, in order to assess the risks associated with consumption of homegrown vegetables. This study aimed to quantify variability in BCFs and evaluate the implications of this variability for human exposure assessments, focusing on cadmium (Cd) and lead (Pb) in lettuce and potatoes sampled around 22 contaminated glassworks sites. In addition, risks associated with measured Cd and Pb concentrations in soil and vegetable samples were characterized and a probabilistic exposure assessment was conducted to estimate the likelihood of local residents exceeding tolerable daily intakes. The results show that concentrations in vegetables were only moderately elevated despite high concentrations in soil, and most samples complied with applicable foodstuff legislation. Still, the daily intake of Cd (but not Pb) was assessed to exceed toxicological thresholds for about a fifth of the study population. Bioconcentration factors were found to vary more than indicated by previous studies, but decreasing BCFs with increasing metal concentrations in the soil can explain why the calculated exposure is only moderately affected by the choice of BCF value when generic soil guideline values are exceeded and the risk may be unacceptable. - Highlights: • Uptake of Cd and Pb by lettuce and potatoes increased with soil contamination. • Consumption of homegrown vegetables may lead to a daily Cd intake above TDIs. • The variability in the calculated BCFs is high when compared to previous studies. • Exposure assessments are most sensitive to the choice of BCFs at low contamination.

  13. Comparative biochemical and pharmacological characterization of the mouse 5HT5A 5-hydroxytryptamine receptor and the human beta2-adrenergic receptor produced in the methylotrophic yeast Pichia pastoris.

    PubMed

    Weiss, H M; Haase, W; Michel, H; Reiländer, H

    1998-03-15

    Over the last few years, Pichia pastoris has been developed into a powerful expression system for a multitude of foreign genes. Here, we demonstrate that the P. pastoris expression system has similar power to the baculovirus expression system in high-level production of two G-protein-coupled receptors, the mouse 5HT5A 5-hydroxtryptamine receptor and the human beta2-adrenergic receptor. Different expression plasmids were constructed in which the cDNAs of the two receptors were cloned under the transcriptional control of the highly inducible promoter of the P. pastoris alcohol oxidase 1 (AOX1) gene. In three expression plasmids, the receptors were fused to the Saccharomyces cerevisiae alpha-factor prepropeptide and also to the c-myc tag or the FLAG tag to permit immunological detection of the receptors. After transformation into P. pastoris strains KM71 and SMD 1163, recombinant clones were selected and tested for the production of the 5HT5A receptor and the beta2-adrenergic receptor by radioligand binding using [N-methyl-3H]lysergic acid diethylamide and [5,7-3H](-)CGP-12177 respectively. The production level of the 5HT5A receptor was improved by a factor of three by fusion with the alpha-factor prepropeptide. Also, the higher gene dosage resulting from multiple insertions of the expression cassette led to an improvement in production by a factor of two for both receptors. The addition of the adrenergic antagonist alprenolol to the culture medium had a positive effect on the number of specific binding sites detectable in clones producing the beta2-adrenergic receptor. For the 5HT5A receptor the addition of yohimbine resulted in a similar but smaller effect. Binding assays revealed that approx. 25 pmol of beta2-adrenergic receptor and approx. 40 pmol of 5HT5A receptor per mg of membrane protein in crude membrane preparations were produced. The pharmacological profiles for the heterologously produced receptors, estimated by ligand-displacement analysis using certain

  14. PHOSPHORUS UPTAKE DYNAMICS AS RELATED TO MATHEMATICAL MODELING OF 'CLADOPHORA' AT A SITE ON LAKE HURON (JOURNAL VERSION)

    EPA Science Inventory

    Cladophora is a significant symptom of eutrophication in Lakes Erie and Ontario and is a local problem associated with nutrient perturbations in Lakes Huron, Michigan, and Superior. This paper presents results of measurements of phosphorus uptake rates as a function of internal p...

  15. 5-Amino-6-chloro-N-[(1-isobutylpiperidin-4-yl)methyl]-2-methylimidazo[1,2-alpha]pyridine-8-carboxamide (CJ-033,466), a novel and selective 5-hydroxytryptamine4 receptor partial agonist: pharmacological profile in vitro and gastroprokinetic effect in conscious dogs.

    PubMed

    Mikami, Tadayoshi; Ochi, Yasuo; Suzuki, Keiko; Saito, Toshiyuki; Sugie, Yutaka; Sakakibara, Minoru

    2008-04-01

    5-Hydroxytryptamine (5-HT) receptors and dopamine(2) (D(2)) receptor modulate gastrointestinal motility. Gastroprokinetic agents that act on several 5-HT receptor subtypes and/or D(2) receptors are used clinically. Although the 5-HT(4) receptor is known to mediate the gastroprokinetic effects of these agents, the absence of highly selective 5-HT(4) receptor agonists has made it difficult to confirm the physiological consequences of selective 5-HT(4) receptor stimulation. In this study, we report the in vitro pharmacological profiles and the in vivo gastroprokinetic effects of 5-amino-6-chloro-N-[(1-isobutylpiperidin-4-yl)methyl]-2-methylimidazo[1,2-alpha]pyridine-8-carboxamide (CJ-033,466), a novel, potent, and selective 5-HT(4) partial agonist. Compared with preceding 5-HT(4) agonists such as cisapride, mosapride, and tegaserod, CJ-033,466 had a superior in vitro profile, with nanomolar agonistic activities for the 5-HT(4) receptor and 1000-fold greater selectivity for the 5-HT(4) receptor over other 5-HT and D(2) receptors. In vivo studies in conscious dogs showed that CJ-033,466 dose-dependently stimulated gastric antral motility in both the fasted and postprandial states at the same dose range and that it was 30 times more potent than cisapride. Furthermore, CJ-033,466 accelerated the gastric emptying rate in a gastroparesis dog model at the minimally effective dose established in the gastric motility study. In conclusion, CJ-033,466 is a potent and highly selective 5-HT(4) agonist that stimulates physiologically coordinated gastric motility, and it has no activity on other 5-HT receptor subtypes and D(2) receptors. Therefore, CJ-033,466 could be used to treat gastroparesis, providing better gastroprokinetics and reduced side effects mediated by the other receptors. PMID:18198343

  16. Contaminant Uptake and Demography of the Loggerhead Shrike (Lanius ludovicianus) at the Lawrence Livermore National Laboratory, Site 300

    SciTech Connect

    van Hattem, M G; Santolo, G

    2005-02-23

    Concentrations of eleven potential environmental contaminants (metals) in the blood and retrice feathers of fledged-Hatch Year and adult loggerhead shrikes (Lanius ludovicianus) were examined at Lawrence Livermore National Laboratory's Site 300 and a control site, in San Joaquin and Contra Costa Counties, California. The purpose of this pilot study was to determine, through non-lethal means, if loggerhead shrikes are exposed to metals at Site 300 and whether specific demographic variables (i.e., clutch size, fledgling success, etc.) are affected. Loggerhead shrikes at Site 300 had higher blood concentrations of metals, especially birds on the west side of the site, when compared to control site birds. Metal concentrations in the feathers of control site birds tended to be higher than Site 300 shrikes. Blood concentrations of metals in loggerhead shrikes from both Site 300 and the control site were well below the Most Tolerant Dietary Level (MTDL) for domestic birds for all metals except selenium. Clutch size was similar to other populations but one deformed embryo was discovered in a failed egg. The results of this pilot study suggest further work is needed to understand possible synergistic effects related to other contaminants of concern found at Site 300 and overall population variability.

  17. Endogenous 5-HT outflow from chicken aorta by 5-HT uptake inhibitors and amphetamine derivatives

    PubMed Central

    DELGERMURUN, Dugar; ITO, Shigeo; OHTA, Toshio; YAMAGUCHI, Soichiro; OTSUGURO, Ken-ichi

    2015-01-01

    Chemoreceptor cells aggregating in clusters in the chicken thoracic aorta contain 5-hydroxytryptamine (5-HT) and have voltage-dependent ion channels and nicotinic acetylcholine receptors, which are characteristics typically associated with neurons. The aim of the present study was to investigate the effects of 5-HT uptake inhibitors, fluvoxamine, fluoxetine and clomipramine (CLM), and amphetamine derivatives, p-chloroamphetamine (PCA) and methamphetamine (MET), on endogenous 5-HT outflow from the isolated chick thoracic aorta in vitro. 5-HT was measured by using a HPLC system with electrochemical detection. The amphetamine derivatives and 5-HT uptake inhibitors caused concentration-dependent increases in endogenous 5-HT outflow. PCA was about ten times more effective in eliciting 5-HT outflow than MET. The 5-HT uptake inhibitors examined had similar potency for 5-HT outflow. PCA and CLM increased 5-HT outflow in a temperature-dependent manner. The outflow of 5-HT induced by PCA or 5-HT uptake inhibitors was independent of extracellular Ca2+ concentration. The 5-HT outflow induced by CLM, but not that by PCA, was dependent on the extracellular NaCl concentration. These results suggest that the 5-HT uptake system of 5-HT-containing chemoreceptor cells in the chicken thoracic aorta has characteristics similar to those of 5-HT-containing neurons in the mammalian central nervous system (CNS). PMID:26321443

  18. Endogenous 5-HT outflow from chicken aorta by 5-HT uptake inhibitors and amphetamine derivatives.

    PubMed

    Delgermurun, Dugar; Ito, Shigeo; Ohta, Toshio; Yamaguchi, Soichiro; Otsuguro, Ken-ichi

    2016-01-01

    Chemoreceptor cells aggregating in clusters in the chicken thoracic aorta contain 5-hydroxytryptamine (5-HT) and have voltage-dependent ion channels and nicotinic acetylcholine receptors, which are characteristics typically associated with neurons. The aim of the present study was to investigate the effects of 5-HT uptake inhibitors, fluvoxamine, fluoxetine and clomipramine (CLM), and amphetamine derivatives, p-chloroamphetamine (PCA) and methamphetamine (MET), on endogenous 5-HT outflow from the isolated chick thoracic aorta in vitro. 5-HT was measured by using a HPLC system with electrochemical detection. The amphetamine derivatives and 5-HT uptake inhibitors caused concentration-dependent increases in endogenous 5-HT outflow. PCA was about ten times more effective in eliciting 5-HT outflow than MET. The 5-HT uptake inhibitors examined had similar potency for 5-HT outflow. PCA and CLM increased 5-HT outflow in a temperature-dependent manner. The outflow of 5-HT induced by PCA or 5-HT uptake inhibitors was independent of extracellular Ca(2+) concentration. The 5-HT outflow induced by CLM, but not that by PCA, was dependent on the extracellular NaCl concentration. These results suggest that the 5-HT uptake system of 5-HT-containing chemoreceptor cells in the chicken thoracic aorta has characteristics similar to those of 5-HT-containing neurons in the mammalian central nervous system (CNS). PMID:26321443

  19. Alterations in dopamine uptake sites and D1 and D2 receptors in cats symptomatic for and recovered from experimental parkinsonism.

    PubMed

    Frohna, P A; Rothblat, D S; Joyce, J N; Schneider, J S

    1995-01-01

    The administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to adult cats severely disrupts the dopaminergic innervation of the striatum. Animals display a parkinson-like syndrome, consisting of akinesia, bradykinesia, postural instability, and rigidity, which spontaneously recovers by 4-6 weeks after the last administration of MPTP. In this study we used quantitative receptor autoradiography to examine changes in DA uptake sites and DA receptors in the basal ganglia of normal, and symptomatic and recovered MPTP-treated cats. Consistent with the destruction of the nigrostriatal DA pathway, there was a severe loss of DA uptake sites, labeled with [3H]-mazindol, in the caudate nucleus (64-82%), nucleus accumbens (44%), putamen (63%), and substantia nigra pars compacta (SNc, 53%) of symptomatic cats. Following behavioral recovery, there were no significant changes in DA uptake site density. Significant increases of [3H]-SCH 23390 binding to D1 DA receptors were observed in the dorsal caudate (> 24%; P < 0.05) of symptomatic cats and in all regions of the caudate-putamen (> 30%; P < 0.05) of recovered animals. [3H]-SCH 23390 binding in the substantia nigra pars reticulata was half of that in the striatum and showed no changes in symptomatic or recovered animals. No alterations in the binding of [125I]-epidepride to D2 receptors was observed in any region of the striatum in either symptomatic or recovered animals. [125I]-Epidepride binding in the SNc was decreased by > 36% (P < 0.05) following MPTP treatment. These data show that cats made parkinsonian by MPTP exposure have a significant decrease in the number of DA reuptake sites throughout the striatum and that recovery of sensorimotor function in these animals is not correlated with an increase in the number of striatal reuptake sites. Behavioral recovery, however, does seem to be correlated with a general elevation of D1 receptors throughout the striatal complex. The present data also

  20. Grass species influence on plant N uptake - Determination of atmospheric N deposition to a semi-natural peat bog site using a 15N labelling approach

    NASA Astrophysics Data System (ADS)

    Hurkuck, Miriam; Brümmer, Christian; Spott, Oliver; Flessa, Heinz; Kutsch, Werner L.

    2014-05-01

    Large areas of natural peat bogs in Northwestern Germany have been converted to arable land and were subjected to draining and peat cutting in the past. The few protected peatland areas remaining are affected by high nitrogen (N) deposition. Our study site - a moderately drained raised bog - is surrounded by highly fertilized agricultural land and livestock production. In this study, we used a 15N pool dilution technique called 'Integrated Total Nitrogen Input' (ITNI) to quantify annual deposition of atmospheric N into biomonitoring pots over a two-year period. Since it considers direct N uptake by plants, it was expected to result in higher N input than conventional methods for determination of N deposition (e.g. micrometeorological approaches, bulk N samplers). Using Lolium multiflorum and Eriophorum vaginatum as monitor plants and low, medium and high levels of fertilization, we aimed to simulate increasing N deposition to planted pots and to allocate airborne N after its uptake by the soil-plant system in aboveground biomass, roots and soil. Increasing N fertilization was positively correlated with biomass production of Eriophorum vaginatum, whereas atmospheric plant N uptake decreased and highest airborne N input of 899.8 ± 67.4 µg N d-1 pot-1 was found for low N fertilization. In contrast, Lolium multiflorum showed a clear dependency of N supply on plant N uptake and was highest (688.7 ± 41.4 µg N d-1 pot-1) for highly fertilized vegetation pots. Our results suggest that grass species respond differently to increasing N input. While crop grasses such as Lolium multiflorum take up N according to N availability, species adopted to nutrient-limited conditions like Eriophorum vaginatum show N saturation effects with increasing N supply. Total airborne N input ranged from about 24 to 66 kg N ha-1 yr-1 dependent on the used indicator plant and the amount of added fertilizer. Parallel determination of atmospheric N deposition using a micrometeorological approach

  1. Increasing Healthy Start food and vitamin voucher uptake for low income pregnant women (Early Years Collaborative Leith Pioneer Site)

    PubMed Central

    Mackenzie, Graham; Dougall, Angela

    2016-01-01

    Poverty has a detrimental impact on health and wellbeing. Healthy Start food and vitamin vouchers provide support for low income families across the UK, but at least 25% of eligible women and children miss out. We set out to increase uptake, with an aim of 90% of eligible women and children (n~540 eligible, varying over time) receiving vouchers in the initial team's catchment area by December 2015. Starting with one midwife and one pregnant woman in March 2014 we used the model for improvement to identify ways to improve documentation, sign up, and referral. Weekly data on process measures and monthly data on voucher receipt were plotted on run charts. Comparing medians for January-June 2014 and March-August 2015 there was a 13.3% rise in voucher receipt in Lothian (increase from 313 to 355 women), versus an 8.4% decline for the rest of Scotland (fall from 1688 to 1546 women). Figures varied by team, influenced by staff, family, and area factors. The initial aim proved unrealistic, as signing up a woman for vouchers increases both the numerator and denominator. Accordingly, the percentage uptake has not increased at a regional level (remains at 75%), though the figure for the initiating team (“team 3” in graphs) has increased from 73.0% (January 2014) to 79.0% (November 2015). We have continued testing, achieving recent increases in the number of women referred for welfare rights advice on benefits, tax credits, employment rights, childcare, and debt, securing on average £4,500 per client during 2015/16 (£404k for 89 clients by mid September 2015). This improvement project, part of the Early Years Collaborative in Scotland, has had a measureable impact on pregnant women across Lothian. Success has relied on testing, an electronic maternity record, rapid dissemination of findings through direct engagement with clinical teams, and persistence. Our findings have relevance across the UK, particularly at a time of worsening finances for many families. PMID

  2. Increasing Healthy Start food and vitamin voucher uptake for low income pregnant women (Early Years Collaborative Leith Pioneer Site).

    PubMed

    Mackenzie, Graham; Dougall, Angela

    2016-01-01

    Poverty has a detrimental impact on health and wellbeing. Healthy Start food and vitamin vouchers provide support for low income families across the UK, but at least 25% of eligible women and children miss out. We set out to increase uptake, with an aim of 90% of eligible women and children (n~540 eligible, varying over time) receiving vouchers in the initial team's catchment area by December 2015. Starting with one midwife and one pregnant woman in March 2014 we used the model for improvement to identify ways to improve documentation, sign up, and referral. Weekly data on process measures and monthly data on voucher receipt were plotted on run charts. Comparing medians for January-June 2014 and March-August 2015 there was a 13.3% rise in voucher receipt in Lothian (increase from 313 to 355 women), versus an 8.4% decline for the rest of Scotland (fall from 1688 to 1546 women). Figures varied by team, influenced by staff, family, and area factors. The initial aim proved unrealistic, as signing up a woman for vouchers increases both the numerator and denominator. Accordingly, the percentage uptake has not increased at a regional level (remains at 75%), though the figure for the initiating team ("team 3" in graphs) has increased from 73.0% (January 2014) to 79.0% (November 2015). We have continued testing, achieving recent increases in the number of women referred for welfare rights advice on benefits, tax credits, employment rights, childcare, and debt, securing on average £4,500 per client during 2015/16 (£404k for 89 clients by mid September 2015). This improvement project, part of the Early Years Collaborative in Scotland, has had a measureable impact on pregnant women across Lothian. Success has relied on testing, an electronic maternity record, rapid dissemination of findings through direct engagement with clinical teams, and persistence. Our findings have relevance across the UK, particularly at a time of worsening finances for many families. PMID:27134747

  3. Site-specific conjugation of single domain antibodies to liposomes enhances photosensitizer uptake and photodynamic therapy efficacy

    NASA Astrophysics Data System (ADS)

    Broekgaarden, M.; van Vught, R.; Oliveira, S.; Roovers, R. C.; van Bergen En Henegouwen, P. M. P.; Pieters, R. J.; van Gulik, T. M.; Breukink, E.; Heger, M.

    2016-03-01

    Photodynamic therapy for therapy-resistant cancers will greatly benefit from targeted delivery of tumor photosensitizing agents. In this study, a strategy for the site-specific conjugation of single domain antibodies onto liposomes containing the photosensitizer zinc phthalocyanine was developed and tested.Photodynamic therapy for therapy-resistant cancers will greatly benefit from targeted delivery of tumor photosensitizing agents. In this study, a strategy for the site-specific conjugation of single domain antibodies onto liposomes containing the photosensitizer zinc phthalocyanine was developed and tested. Electronic supplementary information (ESI) available: Materials and methods. See DOI: 10.1039/c6nr00014b

  4. Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomography

    SciTech Connect

    Schwaiger, M.; Hutchins, G.D.; Kalff, V.; Rosenspire, K.; Haka, M.S.; Mallette, S.; Deeb, G.M.; Abrams, G.D.; Wieland, D. )

    1991-05-01

    Positron emission tomography in combination with the newly introduced catecholamine analogue ({sup 11}C)hydroxyephedrine (({sup 11}C)HED) enables the noninvasive delineation of sympathetic nerve terminals of the heart. To address the ongoing controversy over possible reinnervation of the human transplant, 5 healthy control subjects and 11 patients were studied after cardiac transplant by this imaging approach. Regional ({sup 11}C)HED retention was compared to regional blood flow as assessed by rubidium-82. Transplant patients were divided into two groups. Group I had recent (less than 1 yr, 4.4 +/- 2.3 mo) surgery, while group II patients underwent cardiac transplantation more than 2 yr before imaging (3.5 +/- 1.3 yr). ({sup 11}C)HED retention paralleled blood flow in normals, but was homogeneously reduced in group I. In contrast, group II patients revealed heterogeneous ({sup 11}C)HED retention, with increased uptake in the proximal anterior and septal wall. Quantitative evaluation of ({sup 11}C)HED retention revealed a 70% reduction in group I and 59% reduction in group II patients (P less than 0.001). In group II patients, ({sup 11}C)HED retention reached 60% of normal in the proximal anterior wall. These data suggest the presence of neuronal tissue in the transplanted human heart, which may reflect regional sympathetic reinnervation.

  5. Site-specific conjugation of single domain antibodies to liposomes enhances photosensitizer uptake and photodynamic therapy efficacy.

    PubMed

    Broekgaarden, M; van Vught, R; Oliveira, S; Roovers, R C; van Bergen En Henegouwen, P M P; Pieters, R J; Van Gulik, T M; Breukink, E; Heger, M

    2016-03-17

    Photodynamic therapy for therapy-resistant cancers will greatly benefit from targeted delivery of tumor photosensitizing agents. In this study, a strategy for the site-specific conjugation of single domain antibodies onto liposomes containing the photosensitizer zinc phthalocyanine was developed and tested. PMID:26954515

  6. Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules

    PubMed Central

    Davidge, Kelly S; Singh, Sandip; Bowman, Lesley AH; Tinajero-Trejo, Mariana; Carballal, Sebastián; Radi, Rafael; Poole, Robert K; Dikshit, Kanak; Estrin, Dario A; Marti, Marcelo A; Boechi, Leonardo

    2015-01-01

    Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O 2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels that are partially blocked by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations introduce modifications in both tunnel topologies and affect the incoming ligand capacity to displace retained water molecules at the active site. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site. PMID:26478812

  7. Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules.

    PubMed

    Boron, Ignacio; Bustamante, Juan Pablo; Davidge, Kelly S; Singh, Sandip; Bowman, Lesley Ah; Tinajero-Trejo, Mariana; Carballal, Sebastián; Radi, Rafael; Poole, Robert K; Dikshit, Kanak; Estrin, Dario A; Marti, Marcelo A; Boechi, Leonardo

    2015-01-01

    Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O 2 and (•)NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels that are partially blocked by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify (•)NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, (•)NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations introduce modifications in both tunnel topologies and affect the incoming ligand capacity to displace retained water molecules at the active site. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site. PMID:26478812

  8. SITE SITE DISTURBANCE EFFECTS ON A CLAY SOIL UNDER PINUS RADIATA - ROOT BIOMASS, MYCORRHIZAL COLONISATION, 15AMMONIUM UPTAKE, AND FOLIAR NUTRIENT LEVELS

    EPA Science Inventory

    Timber harvesting can result in adverse physical, chemical and biological alterations to soil. The objective of this study was to examine the effects of site disturbance to determine the extent and duration of possible harvesting impacts on soil chemical and biological propertie...

  9. Did we choose the best one? A new site selection approach based on exposure and uptake potential for waste incineration.

    PubMed

    Demirarslan, K Onur; Korucu, M Kemal; Karademir, Aykan

    2016-08-01

    Ecological problems arising after the construction and operation of a waste incineration plant generally originate from incorrect decisions made during the selection of the location of the plant. The main objective of this study is to investigate how the selection method for the location of a new municipal waste incineration plant can be improved by using a dispersion modelling approach supported by geographical information systems and multi-criteria decision analysis. Considering this aim, the appropriateness of the current location of an existent plant was assessed by applying a pollution dispersion model. Using this procedure, the site ranking for a total of 90 candidate locations and the site of the existing incinerator were determined by a new location selection practice and the current place of the plant was evaluated by ANOVA and Tukey tests. This ranking, made without the use of modelling approaches, was re-evaluated based on the modelling of various variables, including the concentration of pollutants, population and population density, demography, temporality of meteorological data, pollutant type, risk formation type by CALPUFF and re-ranking the results. The findings clearly indicate the impropriety of the location of the current plant, as the pollution distribution model showed that its location was the fourth-worst choice among 91 possibilities. It was concluded that the location selection procedures for waste incinerators should benefit from the improvements obtained by the articulation of pollution dispersion studies combined with the population density data to obtain the most suitable location. PMID:27354016

  10. An evaluation of the regional acid deposition model surface module for ozone uptake at three sites in the San Joaquin Valley of California

    NASA Technical Reports Server (NTRS)

    Massman, W. J.; Pederson, J.; Delany, A.; Grantz, D.; Hertog, G. Den; Neumann, H. H.; Oncley, S. P.; Pearson, R., Jr.; Shaw, R. H.

    1994-01-01

    Plants and soils act as major sinks for the destruction of tropospheric ozone, especially during daylight hours when plant stomata open and are thought to provide the dominant pathway for the uptake of ozone. The present study, part of the California Ozone Deposition Experiment, compares predictions of the regional acid deposition model ozone surface conductance module with surface conductance data derived from eddy covariance measurements of ozone flux taken at a grape, a cotton, and a grassland site in the San Joaquin Valley of California during the summer of 1991. Results indicate that the model (which was developed to provide long-term large-area estimates for the eastern United States) significantly overpredicts the surface conductance at all times of the day for at least two important types of plant cover of the San Joaquin Valley and that it incorrectly partitions the ozone flux between transpiring and nontranspiring components of the surface at the third site. Consequently, the model either overpredicts or inaccurately represents the observed deposition velocities. Other results indicate that the presence of dew does not reduce the rate of ozone deposition, contradicting to model assumptions, and that model assumptions involving the dependency of stomata upon environmental temperature are unnecessary. The effects of measurement errors and biases, arising from the presence of the roughness sublayer and possible photochemical reactions, are also discussed. A simpler model for ozone surface deposition (at least for the San Joaquin Valley) is proposed and evaluated.

  11. An evaluation of the regional acid deposition model surface module for ozone uptake at three sites in the San Joaquin Valley of California

    NASA Astrophysics Data System (ADS)

    Massman, W. J.; Pederson, J.; Delany, A.; Grantz, D.; den Hartog, G.; Neumann, H. H.; Oncley, S. P.; Pearson, R.; Shaw, R. H.

    1994-04-01

    Plants and soils act as major sinks for the destruction of tropospheric ozone, especially during daylight hours when plant stomata open and are thought to provide the dominant pathway for the uptake of ozone. The present study, part of the California Ozone Deposition Experiment, compares predictions of the regional acid deposition model ozone surface conductance module with surface conductance data derived from eddy covariance measurements of ozone flux taken at a grape, a cotton, and a grassland site in the San Joaquin Valley of California during the summer of 1991. Results indicate that the model (which was developed to provide long-term large-area estimates for the eastern United States) significantly overpredicts the surface conductance at all times of the day for at least two important types of plant cover of the San Joaquin Valley and that it incorrectly partitions the ozone flux between transpiring and nontranspiring components of the surface at the third site. Consequently, the model either overpredicts or inaccurately represents the observed deposition velocities. Other results indicate that the presence of dew does not reduce the rate of ozone deposition, contradicting to model assumptions, and that model assumptions involving the dependency of stomata upon environmental temperature are unnecessary. The effects of measurement errors and biases, arising from the presence of the roughness sublayer and possible photochemical reactions, are also discussed. A simpler model for ozone surface deposition (at least for the San Joaquin Valley) is proposed and evaluated.

  12. A serotonergic system in veins: serotonin transporter-independent uptake.

    PubMed

    Linder, A Elizabeth; Ni, Wei; Szasz, Theodora; Burnett, Robert; Diaz, Jessica; Geddes, Timothy J; Kuhn, Donald M; Watts, Stephanie W

    2008-06-01

    We hypothesized that the 5-hydroxytryptamine (5-HT; serotonin) system is present and functional in veins. In vena cava (VC), the presence of the 5-HT synthesis rate-limiting enzyme tryptophan hydroxylase-1 mRNA and accumulation of the 5-HT synthesis intermediate 5-hydroxytryptophan after incubation with tryptophan supported the ability of veins to synthesize 5-HT. The presence of 5-HT and its metabolite 5-hydroxyindole acetic acid was measured by high-performance liquid chromatography in VC and jugular vein (JV), and it was compared with similarly sized arteries aorta (RA) and carotid (CA), respectively. In rats treated with the monoamine oxidase-A (MAO-A) inhibitor pargyline to prevent 5-HT metabolism, basal 5-HT levels were higher in veins than in arteries. 5-HT uptake was observed after exposure to exogenous 5-HT in all vessels. The presence of MAO-A and the 5-HT transporter (SERT) in VC was observed by immunohistochemistry and Western analysis. However, 5-HT uptake was not inhibited by the SERT inhibitors fluoxetine and/or fluvoxamine in VC and JV, as opposed to the inhibition in RA and CA. Moreover, studies performed in VC from mutant rats lacking SERT showed no differences in 5-HT uptake compared with VC from wild type. These data suggest the SERT is not functional under physiological conditions in veins. The differences in 5-HT handling between veins and arteries may represent alternative avenues for targeting the 5-HT system in the peripheral circulation for controlling vascular tone. PMID:18322152

  13. Random and site-specific mutagenesis of the Helicobacter pylori ferric uptake regulator provides insight into Fur structure-function relationships.

    PubMed

    Gilbreath, Jeremy J; Pich, Oscar Q; Benoit, Stéphane L; Besold, Angelique N; Cha, Jeong-Heon; Maier, Robert J; Michel, Sarah L J; Maynard, Ernest L; Merrell, D Scott

    2013-07-01

    The ferric uptake regulator (Fur) of Helicobacter pylori is a global regulator that is important for colonization and survival within the gastric mucosa. H. pylori Fur is unique in its ability to activate and repress gene expression in both the iron-bound (Fe-Fur) and apo forms (apo-Fur). In the current study we combined random and site-specific mutagenesis to identify amino acid residues important for both Fe-Fur and apo-Fur function. We identified 25 mutations that affected Fe-Fur repression and 23 mutations that affected apo-Fur repression, as determined by transcriptional analyses of the Fe-Fur target gene amiE, and the apo-Fur target gene, pfr. In addition, eight of these mutations also significantly affected levels of Fur in the cell. Based on regulatory phenotypes, we selected several representative mutations to characterize further. Of those selected, we purified the wild-type (HpFurWT) and three mutant Fur proteins (HpFurE5A, HpFurA92T and HpFurH134Y), which represent mutations in the N-terminal extension, the regulatory metal binding site (S2) and the structural metal binding site (S3) respectively. Purified proteins were evaluated for secondary structure by circular dichroism spectroscopy, iron-binding by atomic absorption spectrophotometry, oligomerization in manganese-substituted and apo conditions by in vitro cross-linking assays, and DNA binding to Fe-Fur and apo-Fur target sequences by fluorescence anisotropy. The results showed that the N-terminal, S2 and S3 regions play distinct roles in terms of Fur structure-function relationships. Overall, these studies provide novel information regarding the role of these residues in Fur function, and provide mechanistic insight into how H. pylori Fur regulates gene expression in both the iron-bound and apo forms of the protein. PMID:23710935

  14. 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of (/sup 3/H)paroxetine-labeled serotonin uptake sites

    SciTech Connect

    Battaglia, G.; Yeh, S.Y.; O'Hearn, E.; Molliver, M.E.; Kuhar, M.J.; De Souza, E.B.

    1987-09-01

    This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%) in the density of (/sup 3/H)paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of (/sup 3/H)mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals.

  15. Uptake of strontium by chamisa (Chrysothamnus nauseosus) shrub plants growing over a former liquid waste disposal site at Los Alamos National Laboratory

    SciTech Connect

    Fresquez, P.R.; Foxx, T.S.; Naranjo, L. Jr.

    1996-06-01

    A major concern of managers at low-level waste burial site facilities is that plant roots may translocate contaminants up to the soil surface. This study investigates the uptake of strontium ({sup 90}Sr), a biologically mobile element, by chamisa (Chrysothamnus nauseosus), a deep-rooted shrub plant, growing in a former liquid waste disposal site (Solid Waste Management Unit [SWMU] 10-003[c]) at Los Alamos National Laboratory (LANL), Los Alamos, New Mexico. Surface soil samples were also collected from below (understory) and between (interspace) shrub canopies. Both chamisa plants growing over SWMU 10-003(c) contained significantly higher concentrations of {sup 90}Sr than a control plant--one plant, in particular, contained 3.35 x 10{sup 6} Bq kg{sup {minus}1} ash (9.05 x 10{sup 4} pCi g{sup {minus}1} ash) in top-growth material. Similarly, soil surface samples collected underneath and between plants contained {sup 90}Sr concentrations above background and LANL screening action levels (> 218 Bq kg{sup {minus}1} dry [5.90 pCi g{sup {minus}1} dry]); this probably occurred as a result of chamisa plant leaf fall contaminating the soil understory area followed by water and/or winds moving {sup 90}Sr to the soil interspace areas. Although some soil surface migration of {sup 90}Sr from SWMU 10-003(c) has occurred, the level of {sup 90}Sr in sediments collected downstream of SWMU 10-003(c) at the LANL boundary was still within regional (background) concentrations.

  16. Association of {sup 11}C-Methionine PET Uptake With Site of Failure After Concurrent Temozolomide and Radiation for Primary Glioblastoma Multiforme

    SciTech Connect

    Lee, Irwin H.; Piert, Morand; Gomez-Hassan, Diana; Junck, Larry; Rogers, Lisa; Hayman, James; Ten Haken, Randall K.; Lawrence, Theodore S.; Cao Yue; Tsien, Christina

    2009-02-01

    Purpose: To determine whether increased uptake on 11C-methionine-PET (MET-PET) imaging obtained before radiation therapy and temozolomide is associated with the site of subsequent failure in newly diagnosed glioblastoma multiforme (GBM). Methods: Patients with primary GBM were treated on a prospective trial with dose- escalated radiation and concurrent temozolomide. As part of the study, MET-PET was obtained before treatment but was not used for target volume definition. Using automated image registration, we assessed whether the area of increased MET-PET activity (PET gross target volume [GTV]) was fully encompassed within the high-dose region and compared the patterns of failure for those with and without adequate high-dose coverage of the PET-GTV. Results: Twenty-six patients were evaluated with a median follow-up of 15 months. Nineteen of 26 had appreciable (>1 cm{sup 3}) volumes of increased MET-PET activity before treatment. Five of 19 patients had PET-GTV that was not fully encompassed within the high-dose region, and all five patients had noncentral failures. Among the 14 patients with adequately covered PET-GTV, only two had noncentral treatment failures. Three of 14 patients had no evidence of recurrence more than 1 year after radiation therapy. Inadequate PET-GTV coverage was associated with increased risk of noncentral failures. (p < 0.01). Conclusion: Pretreatment MET-PET appears to identify areas at highest risk for recurrence for patients with GBM. It would be reasonable to test a strategy of incorporating MET-PET into radiation treatment planning, particularly for identifying areas for conformal boost.

  17. Roles of uptake, biotransformation, and target site sensitivity in determining the differential toxicity of chlorpyrifos to second to fourth instar Chironomous riparius (Meigen)

    USGS Publications Warehouse

    Buchwalter, D.B.; Sandahl, J.F.; Jenkins, J.J.; Curtis, L.R.

    2004-01-01

    Early life stages of aquatic organisms tend to be more sensitive to various chemical contaminants than later life stages. This research attempted to identify the key biological factors that determined sensitivity differences among life stages of the aquatic insect Chironomous riparius. Specifically, second to fourth instar larvae were exposed in vivo to both low and high waterborne concentrations of chlorpyrifos to examine differences in accumulation rates, chlorpyrifos biotransformation, and overall sensitivity among instars. In vitro acetylcholinesterase (AChE) assays were performed with chlorpyrifos and the metabolite, chlorpyrifos-oxon, to investigate potential target site sensitivity differences among instars. Earlier instars accumulated chlorpyrifos more rapidly than later instars. There were no major differences among instars in the biotransformation rates of chlorpyrifos to the more polar metabolites, chlorpyrifos-oxon, and chlorpyridinol (TCP). Homogenate AChE activities from second to fourth instar larvae were refractory to chlorpyrifos, even at high concentrations. In contrast, homogenate AChE activities were responsive in a dose-dependent manner to chlorpyrifos-oxon. In general, it appeared that chlorpyrifos sensitivity differences among second to fourth instar C. riparius were largely determined by differences in uptake rates. In terms of AChE depression, fourth instar homogenates were more sensitive to chlorpyrifos and chlorpyrifos-oxon than earlier instars. However, basal AChE activity in fourth instar larvae was significantly higher than basal AChE activity in second to third instar larvae, which could potentially offset the apparent increased sensitivity to the oxon. ?? 2003 Elsevier B.V. All rights reserved.

  18. Selective uptake of cholesteryl esters of low-density lipoproteins is mediated by the lipoprotein-binding site in HepG2 cells and is followed by the hydrolysis of cholesteryl esters.

    PubMed Central

    Brissette, L; Charest, M C; Falstrault, L

    1996-01-01

    The study described in this paper shows that 125I-labelled low-density lipoproteins (LDL) interact with high- and low-affinity binding sites on human hepatoma (HepG2) cells. The former site is the LDL receptor and the latter is the lipoprotein-binding site (LBS). The association of 125I-labelled LDL and [3H]cholesteryl ethers-LDL with HepG2 cells revealed a 4-fold selective uptake of cholesteryl esters (CE) in a 4 h incubation period, which correlated with the depletion of CE mass in LDL. This selective uptake was not observed when the cells were incubated in the presence of a 100-fold excess of high-density lipoprotein 3, conditions where only the LDL receptor is being monitored. Also, no reduction in uptake was observed in the presence of IgG-C7, an anti-(LDL receptor) monoclonal antibody. Both findings indicate that the selective uptake occurs through the LBS and that the LBS contributes more to the entry of CE from LDL into the cell than does the LDL receptor. The fates of CE entering the cell via the LDL receptor and the LBS were also followed. To achieve this, LDL were labelled with [3H]cholesteryl oleate and the hydrolysis of [3H]cholesteryl oleate was monitored. The results indicated that 45% of the CE were hydrolysed after a 4 h incubation period, irrespective of the site of entry. Chloroquine (100 microM) was shown to inhibit hydrolysis, indicating that lysosomal enzymes were responsible for the hydrolysis of LDL-CE, whichever pathway was used. Thus our results reveal, for the first time, that the mass of CE entering the cell via the LBS is substantial and that hydrolysis of CE is by lysosomal enzyme activity. Overall, this suggests that the LBS has significant physiological importance. PMID:8836127

  19. Nitrogen-13 glutamate uptake and perfusion in Walker 256 carcinosarcoma before and after single-dose irradiation

    SciTech Connect

    Knapp, W.H.; Helus, F.; Layer, K.; Panzer, M.; Hoever, K.H.O.; Ostertag, H.

    1986-10-01

    Nitrogen-13 (13N) glutamate uptake was recorded in 18 anesthetized rats, both before and at least once after intervention. Each investigation was immediately followed by imaging of blood flow distribution using (11C)butanol. All animals had Walker 256 carcinosarcoma implants in one hind leg. Tumors were locally irradiated with a dose of 800 rad in 14 rats; in four rats, the vasoactive substance 5-hydroxytryptamine (5-HT) was administered. Prior to interventions, the (13N)glutamate tumor-to-muscle uptake showed a linear correlation with blood flow close to identity (y = 0.117 + 0.915x, r = 0.97). After irradiation, a discordant pattern was observed: blood flow tended to increase, while (13N)glutamate tumor-to-muscle uptake dropped from 4.30 +/- 0.66 (s.e.m.) to 3.06 +/- 0.36 (p less than 0.005) during 30 min and attained 4.04 +/- 0.67 2 days later. If (13N)glutamate tumor-to-muscle uptake was related to that of (11C) butanol in each individual animal, this index dropped from 0.93 +/- 0.03 (s.e.m.) to 0.62 +/- 0.04 (p less than 0.001) 30 min after irradiation and attained 0.90 +/- 0.09 after 2 days. In animals treated with 5-HT, (13N)glutamate and (11C)butanol showed a parallel drop from 6.60 +/- 0.84 to 2.10 +/- 0.60 (p less than 0.05) and from 6.8 +/- 0.78 to 2.08 +/- 0.74 (p less than 0.05), respectively. Thus, single-dose irradiation causes (13N)glutamate uptake to be uncoupled with respect to flow, while (13N)glutamate uptake in untreated tumors is flow-limited and responds together with flow on vasomotion.

  20. [C-11]{beta}CNT: A new monoamine uptake ligand for studying serotonin and dopamine transporter sites in the living brain with PET

    SciTech Connect

    Mulholland, G.K.; Zheng, Q.H.; Zhou, F.C.

    1996-05-01

    There is considerable interest in measuring serotonin (5HT) and dopamine (DA) function in the human brain. Altered levels of 5HT and DA are recognized in drug abuse, neurotoxicities, psychiatric disorders, and neurodegenerative conditions including Alzheimer`s and Parkinson`s disease. Several phenyltropane analogs of cocaine bind tightly to both DA and 5HT uptake proteins. We have made a new agent from this class called {beta}CNT, 2{beta}-carboxymethyl-3{beta}-(2-naphthyl)-tropane, the isosteric O-for-CH{sub 2} analog of a compound reported to have among the highest measured affinities for DA and 5HT transporters and studied its in vivo brain distributions in animals for the first time. Optically pure {beta}CNT was made from cocaine, and labeled at the O-methyl position by esterification of {beta}CNT-acid with [C-11]CH{sub 3}OTfl under conditions similar to Wilson`s. HPLC-purified (99+%) final products (15-50% eob yield from CO{sub 2}, 40 min synth) had specific activities 0.1-1.2 Ci/{mu}mol at the time of injection. Preliminary [C-11]{beta}{beta}CNT rodent distribution showed very high brain uptake (3% ID at 60 min) and localization (striat: fr cort: hypo: cer: blood, 11: 5: 4: 1: 06). {beta}CNT-PET studies in juvenile pigs (5-20 mCi, 20-35 kg) found rapid brain uptake, and prominent retention (85 min) in midbrain, anterior brainstem and striatum, followed by cortex and olfactory bulb. Paroxetine pretreatment (5HT uptake blocker, 2mg/kg), diminished retention in most brain areas; nomifensine (DA/NE uptake blocker, 6 mg/kg) reduced striatum selectively. Direct comparisons of [C-11]{beta}CNT with other PET transporter radioligands {beta}CFT, {beta}CIT, and {beta}CTT (RTI-32) in the same pig found {beta}CNT had highest overall brain uptake among the agents. These initial results suggest {beta}CNT has favorable properties for imaging both 5HT and DA transporters in vivo, and further evaluation of its potential as a human PET agent is warranted.

  1. Vascular reactivity, 5-HT uptake, and blood pressure in the serotonin transporter knockout rat.

    PubMed

    Linder, A Elizabeth; Diaz, Jessica; Ni, Wei; Szasz, Theo; Burnett, Robert; Watts, Stephanie W

    2008-04-01

    The handling of serotonin [5-hydroxytryptamine (5-HT)] depends on the serotonin transporter (SERT). A SERT knockout (KO) rat is a useful model to test the hypothesis that SERT is the primary mechanism for arterial 5-HT uptake and to investigate the impact of SERT removal on blood pressure. Wild-type (WT) and KO rats were used to measure 5-HT content (plasma, raphe, aorta, carotid, and mesenteric artery), aortic isometric contraction, and blood pressure. HPLC supported the lack of circulating 5-HT in plasma (ng/ml plasma, WT, 310 +/- 96; and KO, 1.0 +/- 0.5; P < 0.05). Immunohistochemistry and Western blot analyses validated the presence of the SERT protein in the WT rats and a lesser expression in the KO rat. The aorta isolated from KO rats had a normal contraction to phenylephrine and norepinephrine and a normal relaxation to the endothelium-dependent agonist acetylcholine compared with the aorta from WT. In contrast, the potency of 5-HT was increased in the aorta from KO rats compared with WT rats [-log EC(50) (M); WT, 5.71 +/- 0.08; and KO, 6.7 +/- 0.18] and maximum contraction was reduced [%phenylephrine (10 muM) contraction, WT, 113 +/- 6%; and KO, 52 +/- 12%]. 5-HT uptake was reduced but not abolished in arteries of the KO compared with the WT rats. Diurnal mean arterial blood pressure, heart rate, and locomotor activity level of the KO rats were similar to the WT rats. These data suggest that there are other mechanisms of 5-HT uptake in the arteries of the rat and that although the absence of circulating 5-HT and/or SERT function sensitizes arteries to 5-HT, SERT dysfunction does not impair normal blood pressure. PMID:18263707

  2. Significant enhancement of gas uptake capacity and selectivity via the judicious increase of open metal sites and Lewis basic sites within two polyhedron-based metal-organic frameworks.

    PubMed

    Liu, Bing; Yao, Shuo; Shi, Chao; Li, Guanghua; Huo, Qisheng; Liu, Yunling

    2016-02-21

    Two new isomorphous polyhedron-based MOFs ( and ), with dual functionalities of OMSs and LBSs, have been synthesized by using the SBB strategy. By judiciously avoiding the DABCO axial ligand, possesses more OMSs than , and exhibits a significant enhancement of CO2 uptake capacity 210 versus 162 cm(3) g(-1) for at 273 K under 1 bar. PMID:26809833

  3. Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue.

    PubMed

    Ayala-Lopez, Nadia; Jackson, William F; Burnett, Robert; Wilson, James N; Thompson, Janice M; Watts, Stephanie W

    2015-12-01

    Perivascular adipose tissue (PVAT) reduces vasoconstriction to norepinephrine (NE). A mechanism by which PVAT could function to reduce vascular contraction is by decreasing the amount of NE to which the vessel is exposed. PVATs from male Sprague-Dawley rats were used to test the hypothesis that PVAT has a NE uptake mechanism. NE was detected by HPLC in mesenteric PVAT and isolated adipocytes. Uptake of NE (10 μM) in mesenteric PVAT was reduced by the NE transporter (NET) inhibitor nisoxetine (1 μM, 73.68 ± 7.62%, all values reported as percentages of vehicle), the 5-hydroxytryptamine transporter (SERT) inhibitor citalopram (100 nM) with the organic cation transporter 3 (OCT3) inhibitor corticosterone (100 μM, 56.18 ± 5.21%), and the NET inhibitor desipramine (10 μM) with corticosterone (100 μM, 61.18 ± 6.82%). Aortic PVAT NE uptake was reduced by corticosterone (100 μM, 53.01 ± 10.96%). Confocal imaging of mesenteric PVAT stained with 4-[4-(dimethylamino)-styrl]-N-methylpyridinium iodide (ASP(+)), a fluorescent substrate of cationic transporters, detected ASP(+) uptake into adipocytes. ASP(+) (2 μM) uptake was reduced by citalopram (100 nM, 66.68 ± 6.43%), corticosterone (100 μM, 43.49 ± 10.17%), nisoxetine (100 nM, 84.12 ± 4.24%), citalopram with corticosterone (100 nM and 100 μM, respectively, 35.75 ± 4.21%), and desipramine with corticosterone (10 and 100 μM, respectively, 50.47 ± 5.78%). NET protein was not detected in mesenteric PVAT adipocytes. Expression of Slc22a3 (OCT3 gene) mRNA and protein in PVAT adipocytes was detected by RT-PCR and immunocytochemistry, respectively. These end points support the presence of a transporter-mediated NE uptake system within PVAT with a potential mediator being OCT3. PMID:26432838

  4. Polyamine Uptake in Carrot Cell Cultures 1

    PubMed Central

    Pistocchi, Rossella; Bagni, Nello; Creus, José A.

    1987-01-01

    Putrescine and spermidine uptake into carrot (Daucus carota L.) cells in culture was studied. The time course of uptake showed that the two polyamines were very quickly transported into the cells, reaching a maximum absorption within 1 minute. Increasing external polyamine concentrations up to 100 millimolar showed the existence of a biphasic system with different affinities at low and high polyamine concentrations. The cellular localization of absorbed polyamines was such that a greater amount of putrescine was present in the cytoplasmic soluble fraction, while spermidine was mostly present in cell walls. The absorbed polyamines were released into the medium in the presence of increasing external concentrations of the corresponding polyamine or Ca2+. The effects of Ca2+ were different for putrescine and spermidine; putrescine uptake was slightly stimulated by 10 micromolar Ca2+ and inhibited by higher concentrations, while for spermidine uptake there was an increasing stimulation in the Ca2+ concentration range between 10 micromolar and 1 millimolar. La3+ nullified the stimulatory effect of 10 micromolar Ca2+ on putrescine uptake and that of 1 millimolar Ca2+ on spermidine uptake. La3+ at 0.5 to 1 millimolar markedly inhibited the uptake of both polyamines, suggesting that it interferes with the sites of polyamine uptake. Putrescine uptake was affected to a lesser extent by metabolic inhibitors than was spermidine uptake. It is proposed that the entry of polyamines into the cells is driven by the transmembrane electrical gradient, with a possible antiport mechanism between external and internal polyamine molecule. PMID:16665446

  5. An uptake of cationized ferritin by alveolar type I cells in airway-instilled goat lung: distribution of anionic sites on the epithelial surface.

    PubMed

    Atwal, O S; Viel, L; Minhas, K J

    1990-07-01

    The present study has investigated ultrastructural localization of anionic sites on the luminal surface of the alveolar epithelium of goat lung by direct airway instillation of cationized ferritin (CF) in the cranial lobe of the right lung through a bronchoscope. The cationic probe decorated preferentially the luminal plasmalemmal vesicles and plasmalemma proper of alveolar type I cell. This indicated the presence of highly charged anionic microdomains at these binding sites. The ligand was internalized in the free plasmalemmal vesicles of alveolar type I cell within 2 min. Heavy decoration of vesicles at 5 min of perfusion indicated that the amount of CF internalization increased with its concentration in the alveoli. It is suggested that exposure of alveolar surface to several gases of ruminal-origin induces changes in the surface charge of luminal plasmalemma of alveolar type I cells. The significance of these anionic plasmalemmal sites is discussed in relation to the adjustment of osmotic pressure gradient across the alveolar-capillary membrane of the ruminant lung. PMID:2390765

  6. Application of ground bone and sheep manure on soils from two contaminated sites and influence on oat growth, uranium and radium uptake and translocation

    NASA Astrophysics Data System (ADS)

    Abreu, M. M.; Pacheco, A.; Santos, E.; Magalhães, M. C. F.

    2012-04-01

    Past radium and uranium exploitation and processing in Urgeiriça mine and radium processing in Barracão (centre-north of Portugal) led to soils and waters contamination. Most of the soils, located in rural areas, are cultivated for vegetables, fruit trees, and/or pasturage, and the waters used for soils irrigation. The objective of this work was to evaluate the capacity of organic amendments and hydroxiapatite to reduce the soil available fraction of Utotal and 226Ra in soils of two areas after four months of incubation. Influence on oat growth, uranium and radium uptake and translocation was also studied. Pot experiments, under controlled conditions, were undertaken during four months of incubation at 70% of the soil water-holding capacity. Urgeiriça (Urg) and Barracão (Brc) soils containing large concentrations of Utotal (635 and 189 mg/kg, respectively), and 226Ra (2310 and 1770 Bq/kg, respectively) were used. The available fraction of these elements, extracted with ammonium acetate, corresponds to: 90 and 20% of total concentration of uranium and radium, respectively, for Urgeiriça soil, and 19 and 43% of total concentration of uranium and radium, respectively, for Barracão soil. Fine ground bone (FB), sheep manure (OM), and vermicompost (V) single or mixtures were used as amendments. Control (soil) and treatments were made in triplicate: (T1) soil+96 g FB/kg of soil; (T2) soil+168 g OM/kg of soil; (T3) soil+168 g OM/kg of soil+96 g FB/kg of soil; (T4) soil+168 g V/kg of soil. After incubation, soil subsamples were analysed for pH, electric conductivity (EC), and available fractions of Utotal and 226Ra. The remaining soils were used for oat (Avena sativa L.) cultivation. Soils had pH 5.15 (Urg) and 6.04 (Brc), and EC 57.3 µS/cm (Urg) and 36.3 µS/cm (Brc). After incubation soil pH increased to a maximum of 6.82 (Urg) and 7.10 (Brc) in amended samples, and EC showed a large increase (15-19 times) when compared to the control. A decrease of the available

  7. Serotonin (5-hydroxytryptamine) glucuronidation in vitro: assay development, human liver microsome activities and species differences.

    PubMed

    Krishnaswamy, S; Duan, S X; Von Moltke, L L; Greenblatt, D J; Sudmeier, J L; Bachovchin, W W; Court, M H

    2003-02-01

    1. The main purpose was to develop a high-performance liquid chromatography (HPLC)-based method to assay serotonin glucuronidation activity using liver microsomal fractions. Application of this method was then demonstrated by determining serotonin UDP-glucuronosyltransferase (UGT) enzyme kinetics using human liver microsomes and recombinant human UGT1A6. Interspecies differences were also evaluated using liver microsomes from 10 different mammalian species. 2. Incubation of liver microsomes with serotonin, UDP-glucuronic acid and magnesium resulted in the formation of a single product peak using HPLC with fluorescence and ultraviolet absorbance detection. This peak was confirmed as serotonin glucuronide based on sensitivity to beta-glucuronidase and by obtaining the expected mass of 352 with positive-ion mass spectrometry. 3. Following a preparative HPLC isolation, the structure of this metabolite was established as serotonin-5-O-glucuronide by (1)H-NMR spectroscopy. 4. Enzyme kinetic studies showed apparent K(m) and V(max) of 8.8 +/- 0.3 mM and 43.4 +/- 0.4 nmoles min(-1) mg(-1) protein, respectively, for human liver microsomes, and 5.9 +/- 0.2 mM and 15.8 +/- 0.2 nmoles min(-1) mg(-1), respectively, for recombinant UGT1A6. 5. The order of serotonin-UGT activities in animal liver microsomes was rat > mouse > human > cow > pig > horse > dog > rabbit > monkey > ferret. Cat livers showed no serotonin-UGT activity. Heterozygous and homozygous mutant Gunn rat livers had 40 and 13%, respectively, of the activity of the normal Wistar rat, indicating a significant contribution by a rat UGT1A isoform to serotonin glucuronidation. 6. This assay provides a novel sensitive and specific technique for the measurement of serotonin-UGT activity in vitro. PMID:12623759

  8. Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues.

    PubMed

    Kärkkäinen, J; Forsström, T; Tornaeus, J; Wähälä, K; Kiuru, P; Honkanen, A; Stenman, U H; Turpeinen, U; Hesso, A

    2005-01-01

    Bufotenine and N,N-dimethyltryptamine (DMT) are hallucinogenic dimethylated indolethylamines (DMIAs) formed from serotonin and tryptamine by the enzyme indolethylamine N-methyltransferase (INMT) ubiquitously present in non-neural tissues. In mammals, endogenous bufotenine and DMT have been identified only in human urine. The DMIAs bind effectively to 5HT receptors and their administration causes a variety of autonomic effects, which may reflect their actual physiological function. Endogenous levels of bufotenine and DMT in blood and a number of animal and human tissues were determined using highly sensitive and specific quantitative mass spectrometric techniques. A new finding was the detection of large amounts of bufotenine in stools, which may be an indication of its role in intestinal function. It is suggested that fecal and urinary bufotenine originate from epithelial cells of the intestine and the kidney, respectively, although the possibility of their synthesis by intestinal bacteria cannot be excluded. Only small amounts of the DMIAs were found in somatic or neural tissues and none in blood. This can be explained by rapid catabolism of the DMIAs by mitochondrial monoamino-oxidase or by the fact that the dimethylated products of serotonin and tryptamine are not formed in significant amounts in most mammalian tissues despite the widespread presence of INMT in tissues. PMID:16095048

  9. The 5-hydroxytryptamine4 receptor enables differentiation of informational content and encoding in the hippocampus.

    PubMed

    Twarkowski, Hannah; Hagena, Hardy; Manahan-Vaughan, Denise

    2016-07-01

    Long-term synaptic plasticity, represented by long-term depression (LTD) and long-term potentiation (LTP) comprise cellular processes that enable memory. Neuromodulators such as serotonin regulate hippocampal function, and the 5-HT4 -receptor contributes to processes underlying cognition. It was previously shown that in the CA1-region, 5-HT4 -receptors regulate the frequency-response relationship of synaptic plasticity: patterned afferent stimulation that has no effect on synaptic strength (i.e., a θm-frequency), will result in LTP or LTD, when given in the presence of a 5-HT4 -agonist, or antagonist, respectively. Here, we show that in the dentate gyrus (DG) and CA3 regions of freely behaving rats, pharmacological manipulations of 5-HT4 -receptors do not influence responses generated at θm-frequencies, but activation of 5-HT4 -receptors prevents persistent LTD in mossy fiber (mf)-CA3, or perforant path-DG synapses. Furthermore, the regulation by 5-HT4 -receptors of LTP is subfield-specific: 5-HT4 -receptor-activation prevents mf-CA3-LTP, but does not strongly affect DG-potentiation. These data suggest that 5-HT4 -receptor activation prioritises information encoding by means of LTP in the DG and CA1 regions, and suppresses persistent information storage in mf-CA3 synapses. Thus, 5-HT4 -receptors serve to shape information storage across the hippocampal circuitry and specify the nature of experience-dependent encoding. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:26800645

  10. 5-hydroxytryptamine and Lyme disease. Opportunity for a novel therapy to reduce the cerebellar tremor?

    PubMed

    Maximov, G K; Maximov, K G; Chokoeva, A A; Lotti, T; Wollina, U; Patterson, J W; Guarneri, C; Tana, C; Fioranelli, M; Roccia, M G; Kanazawa, N; Tchernev, G

    2016-01-01

    Lyme boreliosis is caused by the spirochete Borrelia burdorferi, which is transmitted by ticks. A 59 year-old woman developed pyrexia, strong headaches, ataxia, dysarthria and tremor of the limbs after a tick bite. She was unable to work and eat on her own. She was hospitalized three times and diagnosed with cerebellar intention tremor, cerebellar ataxia, dysarthria, bilateral horizontal gaze paralysis and a central lesion of the left facial nerve. There were no pyramidal, sensory or psychiatric disturbances. The brain MRI showed multifocal leucoencephalopathy with many hyperintense areas in both hemispheres, as well as in the left superior pedunculus cerebellaris. Diagnosis was confirmed by serologic examination. Treatment with cephtriaxone, doxycycline, methylprednisolone, cephixime and ciprofloxacine was administered without effect on the tremor, ataxia and horizontal gaze paralysis. Treatment was then administered with 5-hydroxytriptamine (5-HT) in increased doses. The result of the three-month treatment with 5-HT was a gradual diminution of the tremor and the ataxia and an increase in the ability to eat, walk and work independently. PMID:27373127

  11. Enhanced 5-hydroxytryptamine (5-HT) release from vascular adrenergic nerves in spontaneously hypertensive rats

    SciTech Connect

    Kawasaki, H.; Urabe, M.; Takasaki, K.

    1986-03-01

    The release of 5-HT from vascular adrenergic nerves was compared between normotensive Wistar Kyoto rats (WKY) and SHR. The mesenteric vascular bed isolated from WKY and SHR was perfused with Krebs solution at a constant flow rate of 5 ml/min. Periarterial nerve stimulation (PNS) was delivered at 4 to 16 Hz for 30 sec. In the SHR preparation, the pressor response to PNS, previously decreased by prazonsin (50 nM), was greatly potentiated after treatment with 5-HT(1 ..mu..M) for 15 min and a frequency-dependent pressor response to PNS reappeared, whereas the 5-HT treatment did not alter the pressor response to exogenous norepinephrine (1 nmol) previously reduced by prazonsin. The potentiation of pressor response to PNS after 5-HT treatment was small in the WKY preparation. This potentiation in both WKY and SHR did not occur in the presence of ketanserin (10 nM). In the preparation labeled with (/sup 3/H)-5-HT, PNS (4-16 Hz) evoked a frequency-dependent increase of (/sup 3/H)-efflux, which was abolished by treatment with tetrodotoxin (100 nM) or 6-hydroxydopamine (50 mg/kg i.p. x 2) and in calcium-free Krebs solution. The PNS evoked-(/sup 3/H)-efflux was much greater in SHR than WKY. These results suggest that the release of 5-HT from vascular adrenergic nerves by PNS is enhanced in the SHR preparation.

  12. The chemical coding of 5-hydroxytryptamine containing enteroendocrine cells in the mouse gastrointestinal tract.

    PubMed

    Reynaud, Yohan; Fakhry, Josiane; Fothergill, Linda; Callaghan, Brid; Ringuet, Mitchell; Hunne, Billie; Bravo, David M; Furness, John B

    2016-06-01

    The majority of 5-HT (serotonin) in the body is contained in enteroendocrine cells of the gastrointestinal mucosa. From the time of their discovery over 80 years ago, the 5-HT-containing cells have been regarded as a class of cell that is distinct from enteroendocrine cells that contain peptide hormones. However, recent studies have cast doubt on the concept of there being distinct classes of enteroendocrine cells, each containing a single hormone or occasionally more than one hormone. Instead, data are rapidly accumulating that there are complex patterns of colocalisation of hormones that identify multiple subclasses of enteroendocrine cells. In the present work, multiple labelling immunohistochemistry is used to investigate patterns of colocalisation of 5-HT with enteric peptide hormones. Over 95 % of 5-HT cells in the duodenum also contained cholecystokinin and about 40 % of them also contained secretin. In the jejunum, about 75 % of 5-HT cells contained cholecystokinin but not secretin and 25 % contained 5-HT plus both cholecystokinin and secretin. Small proportions of 5-HT cells contained gastrin or somatostatin in the stomach, PYY or GLP-1 in the small intestine and GLP-1 or somatostatin in the large intestine. Rare or very rare 5-HT cells contained ghrelin (stomach), neurotensin (small and large intestines), somatostatin (small intestine) and PYY (in the large intestine). It is concluded that 5-HT-containing enteroendocrine cells are heterogeneous in their chemical coding and by implication in their functions. PMID:26803512

  13. Potential Moderating Effects of Selenium on Mercury Uptake and Selenium:Mercury Molar Ratios in Fish From Oak Ridge and Savannah River Site - 12086

    SciTech Connect

    Burger, Joanna; Gochfeld, Michael; Donio, Mark; Jeitner, Christian; Pittfield, Taryn

    2012-07-01

    Mercury contamination is an important remediation issue at the U.S. Department of Energy's (DOE) Oak Ridge Reservation and to a lesser extent at other DOE sites because of the hazard it presents, potential consequences to humans and eco-receptors, and completed pathways, to offsite receptors. Recent work has emphasized that selenium might ameliorate the toxicity of mercury, and we examine the selenium:mercury (Se:Hg) molar ratios in fish from Oak Ridge, and compare them to Se:Hg molar ratios in fish from the Savannah River. Selenium/mercury molar ratios varied considerably among and within fish species. There was considerable variation in the molar ratios for individual fish (as opposed to mean ratios by species) for freshwater fish from both sites. The inter-individual variation in molar ratios indicates that such that the molar ratios of mean Se and Hg concentrations may not be representative. Even for fish species with relatively low mercury levels, some individual fish have molar ratios less than unity, the value sometime thought to be protective. Selenium levels varied narrowly regardless of fish size, consistent with homeostatic regulation of this essential trace element. The data indicate that considerable attention will need to be directed toward variations and variances, as well as the mechanisms of the interaction of selenium and mercury, before risk assessment and risk management policies can use this information to manage mercury pollution and risk. Even so, if there are high levels of selenium in the fish from Poplar Creek on Oak Ridge, then the potential exists for some amelioration of adverse health effects, on the fish themselves, predators that eat them, and people who consume them. This work will aid DOE because it will allow managers and scientists to understand another aspect that affects fate and transport of mercury, as well as the potential effects of methylmercury in fish for human and ecological receptors. The variability within fish

  14. Cystathionine γ lyase-hydrogen sulfide increases peroxisome proliferator-activated receptor γ activity by sulfhydration at C139 site thereby promoting glucose uptake and lipid storage in adipocytes.

    PubMed

    Cai, Junyan; Shi, Xiaoqin; Wang, Huamin; Fan, Jinghui; Feng, Yongliang; Lin, Xianjuan; Yang, Jichun; Cui, Qinghua; Tang, Chaoshu; Xu, Guoheng; Geng, Bin

    2016-05-01

    Adipocytes express the cystathionine γ lyase (CSE)-hydrogen sulfide (H2S) system. CSE-H2S promotes adipogenesis but ameliorates adipocyte insulin resistance. We investigated the mechanism of how CSE-H2S induces these paradoxical effects. First, we confirmed that an H2S donor or CSE overexpression promoted adipocyte differentiation. Second, we found that H2S donor inhibited but CSE inhibition increased phosphodiesterase (PDE) activity. H2S replacing isobutylmethylxanthine in the differentiation program induced adipocyte differentiation in part. Inhibiting PDE activity by H2S induced peroxisome proliferator activated receptor γ (PPARγ) protein and mRNA expression. Of note, H2S directly sulfhydrated PPARγ protein. Sulfhydrated PPARγ increased its nuclear accumulation, DNA binding activity and adipogenesis gene expression, thereby increasing glucose uptake and lipid storage, which were blocked by the desulfhydration reagent DTT. H2S induced PPARγ sulfhydration, which was blocked by mutation of the C139 site of PPARγ. In mice fed a high-fat diet (HFD) for 4 weeks, the CSE inhibitor decreased but H2S donor increased adipocyte numbers. In obese mice fed an HFD for 13 weeks, H2S treatment increased PPARγ sulfhydration in adipose tissues and attenuated insulin resistance but did not increase obesity. In conclusion, CSE-H2S increased PPARγ activity by direct sulfhydration at the C139 site, thereby changing glucose into triglyceride storage in adipocytes. CSE-H2S-mediated PPARγ activation might be a new therapeutic target for diabetes associated with obesity. PMID:26946260

  15. Uptake As Language Awareness.

    ERIC Educational Resources Information Center

    Ellis, Rod

    1995-01-01

    Investigates the sincerity and validity of uptake as a measure of language learning by comparing the words students report they have learned after completing a listening task with the words they score correctly on a translation test. Results indicate that whereas uptake may have construct validity, its concurrent validity is uncertain. (16…

  16. Iodine 125-lysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial cells

    SciTech Connect

    Yagaloff, K.A.; Hartig, P.R.

    1985-12-01

    /sup 125/I-Lysergic acid diethylamide (/sup 125/I-LSD) binds with high affinity to serotonergic sites on rat choroid plexus. These sites were localized to choroid plexus epithelial cells by use of a novel high resolution stripping film technique for light microscopic autoradiography. In membrane preparations from rat choroid plexus, the serotonergic site density was 3100 fmol/mg of protein, which is 10-fold higher than the density of any other serotonergic site in brain homogenates. The choroid plexus site exhibits a novel pharmacology that does not match the properties of 5-hydroxytryptamine-1a (5-HT1a), 5-HT1b, or 5-HT2 serotonergic sites. /sup 125/I-LSD binding to the choroid plexus site is potently inhibited by mianserin, serotonin, and (+)-LSD. Other serotonergic, dopaminergic, and adrenergic agonists and antagonists exhibit moderate to weak affinities for this site. The rat choroid plexus /sup 125/I-LSD binding site appears to represent a new type of serotonergic site which is located on non-neuronal cells in this tissue.

  17. Radioactive iodine uptake

    MedlinePlus

    ... uptake may be due to: Factitious hyperthyroidism Iodine overload Subacute thyroiditis Silent (or painless) thyroiditis Amiodarone Risks ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  18. Methane uptake in forest and agro-ecosystems in Australia

    NASA Astrophysics Data System (ADS)

    Arndt, S. K.; Livesley, S. J.; Fest, B. J.; Weston, C. J.; Butterbach-Bahl, K.

    2007-12-01

    Oxidation of methane by methanotrophic bacteria in aerated soils does provide a considerable global sink for greenhouse gases (-30 Tg CH4/yr). The form of land-use can have a significant impact on the methane uptake capacity of a soil. We investigated the sink strength for methane uptake of forest ecosystems and agro- ecosystems in Australia using automated measurement systems and manual chamber methods. Our results demonstrate large differences in the methane uptake capacity of Australian soils. Data from Western Australia showed that CH4 uptake rates increased with stand age of plantations and were greatest in an undisturbed native forest and lowest in an improved pasture. Measurements in differently aged forest ecosystems indicated that sites with the most recent fire disturbance had the lowest methane uptake rates. Generally, native forest ecosystems showed the greatest methane uptake rates (up to 130 kg CO2-e ha yr). Plantations (eucalyptus/pine) showed significantly lower methane uptake rates (around 15 kg CO2-e ha yr). Grazed pastures in Australia had the lowest uptake rates (6 kg CO2-e ha yr) and were occasional methane sources. The methane uptake rates of soils were only marginally influenced by environmental parameters over the course of a year. Between sites the methane uptake rates were not related to soil parameters such as soil bulk density. Experiments with excavated soil cores demonstrated that diffusivity of methane through the upper soil layer was the rate limiting step. Our results indicate that the community structure of methanotrophic bacteria and substrate diffusivity are the most important factor influencing methane uptake rates in soils. Disturbance events such as change of land-use or vegetation structure can have significant impacts on the capacity of soils to take up methane.

  19. Putrescine uptake in saintpaulia petals.

    PubMed

    Bagni, N; Pistocchi, R

    1985-02-01

    Putrescine uptake and the kinetics of this uptake were studied in petals of Saintpaulia ionantha Wendl. Uptake experiments of [(3)H] or [(14)C] putrescine were done on single petals at room temperature at various pH values. The results show that putrescine uptake occurs against a concentration gradient at low external putrescine concentration (0.5-100 micromolar) and follows a concentration gradient at higher external putrescine concentrations (100 micromolar to 100 millimolar). 2,4-Dinitrophenol and carbonylcyanide-m-chlorophenylhydrazone, two uncouplers, had no effect on putrescine uptake. Uptake rates were constant for 2 hours, reaching a maximum after 3 to 4 hours. Putrescine uptake depended markedly on the external pH and two maxima were observed: at low external concentrations of putrescine, the optimum was at pH 5 to 5.5; at higher concentrations the optimum was at pH 8. PMID:16664065

  20. Endocytotic uptake of nutrients in carnivorous plants.

    PubMed

    Adlassnig, Wolfram; Koller-Peroutka, Marianne; Bauer, Sonja; Koshkin, Edith; Lendl, Thomas; Lichtscheidl, Irene K

    2012-07-01

    Carnivorous plants trap, digest and absorb animals in order to supplement their mineral nutrition. Nutrients absorbed by the plant include different nitrogen species, phosphate, potassium, trace elements and small organic compounds. Uptake is usually thought to be performed via specific channels, but this study provides evidence that endocytosis is involved as well. Traps of the carnivorous plants Nepenthes coccinea, Nepenthes ventrata, Cephalotus follicularis, Drosophyllum lusitanicum, Drosera capensis, Dionaea muscipula, Aldrovanda vesiculosa, Genlisea violacea × lobata, Sarracenia psittacina and Sarracenia purpurea were stained with methylene blue in order to identify possible sites of uptake. The permeable parts of the traps were incubated with fluorescein isothiocyanate labelled bovine serum albumin (FITC-BSA) and other fluorescent endocytosis markers, combined with the soluble protein BSA or respiratory inhibitors. Uptake was studied by confocal microscopy. In Nepenthes, small fluorescent vesicles became visible 1 h after incubation with FITC-BSA. These vesicles fused to larger compartments within 30 h. A similar behaviour was found in the related genera Drosera, Dionaea, Aldrovanda and Drosophyllum but also in Cephalotus with glands of different evolutionary origin. In Genlisea and Sarracenia, no evidence for endocytosis was found. We propose that in many carnivorous plants, nutrient uptake by carriers is supplemented by endocytosis, which enables absorption and intracellular digestion of whole proteins. The advantage for the plant of reducing secretion of enzymes for extracellular digestion is evident. PMID:22417315

  1. Phospholipase A2 and 3H-hemicholinium-3 binding sites in rat brain: A potential second-messenger role for fatty acids in the regulation of high-affinity choline uptake

    SciTech Connect

    Saltarelli, M.D.; Yamada, K.; Coyle, J.T. )

    1990-01-01

    The involvement of phospholipase A2 (PLA2) and fatty acid release in the regulation of sodium-dependent high-affinity choline uptake in rat brain was assessed in vitro through the use of the specific binding of 3H-hemicholinium-3 (3H-HCh-3). Addition of arachidonic acid and other unsaturated fatty acids to rat striatal membranes in vitro resulted in a dose-dependent, temperature-independent activation of 3H-HCh-3 binding. Scatchard analysis revealed that these changes in binding result from a 2-fold increase in the affinity and capacity of 3H-HCh-3 binding. Saturated fatty acids, lysophospholipids, and phospholipids did not affect specific 3H-HCh-3 binding. Addition of defatted BSA to membranes, which had been treated previously with arachidonic acid, completely reversed the increase in specific 3H-HCh-3 binding. However, several inhibitors of fatty acid metabolism, including nordihydroguaiaretic acid, indomethacin, catalase, and superoxide dismutase, did not alter arachidonic acid-induced changes in 3H-HCh-3 binding, suggesting that unsaturated fatty acids, and not their metabolites, are directly responsible for the observed activation of specific 3H-HCh-3 binding. Additionally, unsaturated fatty acids dose-dependently inhibited high-affinity 3H-choline uptake in rat striatal synaptosomes, apparently due to the disruption of synaptosomal integrity. The phospholipase A2 inhibitors quinacrine hydrochloride, trifluoperazine, and 4-bromophenacylbromide dose-dependently inhibited potassium depolarization-induced activation of specific 3H-HCh-3 binding in slices of rat brain in vitro. Similarly, both quinacrine and trifluoperazine inhibited the metabolism of phospholipids and the release of fatty acids evoked by either elevated KCl or calcium ionophore A23187.

  2. The effects of nabumetone, a cyclooxygenase-2 inhibitor, on cisplatin-induced 5-hydroxytryptamine release from the isolated rat ileum.

    PubMed

    Kudo, C; Minami, M; Hirafuji, M; Endo, T; Hamaue, N; Akita, K; Murakami, T; Kawaguchi, H

    2001-01-01

    In order to elucidate 5-HT release influenced by PGE2 in the background of the anticancer drug-induced emesis, the effect of nabumetone, a COX-2 inhibitor, on the release of 5-HT from the isolated rat ileum was investigated. PGE2 produced a concentration-dependent increase (10(-9) to 10 M) and decrease (10(-8) to 10(-6) M) in 5-HT release. Arachidonic acid also demonstrated a similar bell-shaped 5-HT release. The arachidonic acid-induced 5-HT release at 3 x 10(-6) M (313.04 +/- 25.90%) was significantly inhibited by the concomitant perfusion with BRL10720 (10(-6) M) (161.98 +/- 19.4%, p<0.01), an active metabolite of nabumetone, or indomethacin (3 x 10(-7) M)(190.01 +/- 16.19%, p<0.05). BRL10720 (10(-6) M)(428.57 +/- 51.72%, p<0.05) significantly inhibited the increase in 5-HT release induced by cisplatin (10(-6) M)(748.56 +/- 136.31%), suggesting that PGE2would be involved in cisplatin-induced 5-HT release. The increase in 5-HT release from the isolated ileum 72 hrs after cisplatin administration, in a delayed-emesis animal model, was significantly inhibited by the in vivo 3-day administration of nabumetone or BRL10720, but was not affected by the 3-day administration of dexamethasone. After 72 hours, however, the in vivo 3-days administration of nabumetone, BRL10720 or dexamethasone had no effect on the increase in ileal 5-HT levels induced by cisplatin. The use of COX-2 inhibitors to ameliorate delayed emesis induced by cisplatin-based anticancer chemotherapy has been proposed. On the other hand, there is a possibility that dexamethasone works through a mechanism other than 5-HT release in delayed emesis. PMID:12090350

  3. 5-Hydroxytryptamine1A receptor-activation hyperpolarizes pyramidal cells and suppresses hippocampal gamma oscillations via Kir3 channel activation

    PubMed Central

    Johnston, April; McBain, Chris J; Fisahn, André

    2014-01-01

    Rhythmic cortical neuronal oscillations in the gamma frequency band (30–80 Hz, gamma oscillations) have been associated with cognitive processes such as sensory perception and integration, attention, learning, and memory. Gamma oscillations are disrupted in disorders for which cognitive deficits are hallmark symptoms such as schizophrenia and Alzheimer's disease. In vitro, various neurotransmitters have been found to modulate gamma oscillations. Serotonin (5-HT) has long been known to be important for both behavioural and cognitive functions such as learning and memory. Multiple 5-HT receptor subtypes are expressed in the CA3 region of the hippocampus and high doses of 5-HT reduce the power of induced gamma oscillations. Hypothesizing that 5-HT may have cell- and receptor subtype-specific modulatory effects, we investigated the receptor subtypes, cell types and cellular mechanisms engaged by 5-HT in the modulation of gamma oscillations in mice and rats. We found that 5-HT decreases the power of kainate-induced hippocampal gamma oscillations in both species via the 5-HT1A receptor subtype. Whole-cell patch clamp recordings demonstrated that this decrease was caused by a hyperpolarization of CA3 pyramidal cells and a reduction of their firing frequency, but not by alteration of inhibitory neurotransmission. Finally, our results show that the effect on pyramidal cells is mediated via the G protein-coupled receptor inwardly rectifying potassium channel Kir3. Our findings suggest this novel cellular mechanism as a potential target for therapies that are aimed at alleviating cognitive decline by helping the brain to maintain or re-establish normal gamma oscillation levels in neuropsychiatric and neurodegenerative disorders. PMID:25107925

  4. In vivo modulation of vagal-identified dorsal medullary neurones by activation of different 5-Hydroxytryptamine2 receptors in rats

    PubMed Central

    Sévoz-Couche, Caroline; Spyer, K Michael; Jordan, David

    2000-01-01

    In in vivo experiments, DOI (a 5-HT2 receptor agonist), MK-212 (a 5-HT2C receptor agonist), and BW-723C86 (a 5-HT2B receptor agonist) were applied by ionophoresis to neurones in the rat nucleus tractus solitarius (NTS) receiving vagal afferent input. The majority of the putative ‘monosynaptically' vagal activated cells were inhibited by both MK-212 (4/6) and DOI (2/4), but unaffected by BW-723C86 (12/14). In contrast, ‘polysynaptically' activated NTS cells were excited by both BW-723C86 (13/19) and DOI (9/10). Inactive ‘intermediate' cells were inhibited by BW-723C86 (9/12), MK-212 (5/6) and DOI (3/4), whilst active cells of this group were excited by BW-723C86 (7/13) and DOI (5/5). The selective 5-HT2B receptor antagonist LY-202715 significantly reduced the excitatory actions of BW-723C86 on ‘intermediate' and ‘polysynaptic' cells (13/13), but not the inhibitory effects observed on inactive Group 2 cells (n=5) whereas the selective 5-HT2C receptor antagonist RS-102221 reversed the inhibitory effects of MK-212 and DOI on ‘monosynaptic and ‘intermediate' neurones. Cardio-pulmonary afferent stimulation inhibited two of four putative ‘monosynaptically' activated calls and all four inactive intermediate cells. These were also inhibited by DOI and MK-212. In contrast, cardio-pulmonary afferents excited all five active intermediate cells and all six putative ‘polysynaptically' activated NTS cells, while all were also previously excited by BW-723C86 and/or DOI. In conclusion, these data demonstrate that neurones in the NTS are affected differently by 5-HT2 receptor ligands, in regard of their vagal postsynaptic location, the type of cardio-pulmonary afferent they receive and the different 5-HT2 receptors activated. PMID:11090119

  5. Understanding uptake of continuous quality improvement in Indigenous primary health care: lessons from a multi-site case study of the Audit and Best Practice for Chronic Disease project

    PubMed Central

    2010-01-01

    Background Experimentation with continuous quality improvement (CQI) processes is well underway in Indigenous Australian primary health care. To date, little research into how health organizations take up, support, and embed these complex innovations is available on which services can draw to inform implementation. In this paper, we examine the practices and processes in the policy and organisational contexts, and aim to explore the ways in which they interact to support and/or hinder services' participation in a large scale Indigenous primary health care CQI program. Methods We took a theory-driven approach, drawing on literature on the theory and effectiveness of CQI systems and the Greenhalgh diffusion of innovation framework. Data included routinely collected regional and service profile data; uptake of tools and progress through the first CQI cycle, and data collected quarterly from hub coordinators on their perceptions of barriers and enablers. A total of 48 interviews were also conducted with key people involved in the development, dissemination, and implementation of the Audit and Best Practice for Chronic Disease (ABCD) project. We compiled the various data, conducted thematic analyses, and developed an in-depth narrative account of the processes of uptake and diffusion into services. Results Uptake of CQI was a complex and messy process that happened in fits and starts, was often characterised by conflicts and tensions, and was iterative, reactive, and transformational. Despite initial enthusiasm, the mixed successes during the first cycle were associated with the interaction of features of the environment, the service, the quality improvement process, and the stakeholders, which operated to produce a set of circumstances that either inhibited or enabled the process of change. Organisations had different levels of capacity to mobilize resources that could shift the balance toward supporting implementation. Different forms of leadership and organisational

  6. Recombinant glucose uptake system

    DOEpatents

    Ingrahm, Lonnie O.; Snoep, Jacob L.; Arfman, Nico

    1997-01-01

    Recombinant organisms are disclosed that contain a pathway for glucose uptake other than the pathway normally utilized by the host cell. In particular, the host cell is one in which glucose transport into the cell normally is coupled to PEP production. This host cell is transformed so that it uses an alternative pathway for glucose transport that is not coupled to PEP production. In a preferred embodiment, the host cell is a bacterium other than Z. mobilis that has been transformed to contain the glf and glk genes of Z. mobilis. By uncoupling glucose transport into the cell from PEP utilization, more PEP is produced for synthesis of products of commercial importance from a given quantity of biomass supplied to the host cells.

  7. Vacuolar Ca(2+) uptake.

    PubMed

    Pittman, Jon K

    2011-08-01

    Calcium transporters that mediate the removal of Ca(2+) from the cytosol and into internal stores provide a critical role in regulating Ca(2+) signals following stimulus induction and in preventing calcium toxicity. The vacuole is a major calcium store in many organisms, particularly plants and fungi. Two main pathways facilitate the accumulation of Ca(2+) into vacuoles, Ca(2+)-ATPases and Ca(2+)/H(+) exchangers. Here I review the biochemical and regulatory features of these transporters that have been characterised in yeast and plants. These Ca(2+) transport mechanisms are compared with those being identified from other vacuolated organisms including algae and protozoa. Studies suggest that Ca(2+) uptake into vacuoles and other related acidic Ca(2+) stores occurs by conserved mechanisms which developed early in evolution. PMID:21310481

  8. Uptake of VOC by sunflower

    NASA Astrophysics Data System (ADS)

    Folkers, A.; Miebach, M.; Kleist, E.; Wildt, J.

    2003-04-01

    To study potential VOC uptake by plants we exposed sunflower (Helianthus annuus) to different VOC in continuously stirred tank reactors. For many VOC like methanol, ethanol, acetone, methylvinylketone, isoprene or limonene no uptake was detectable within the accuracy of our analytic set up. Other VOC like hexanal, octanal, (E)-3-hexenol and nopinone were taken up by sunflower. The uptake was related to stomatal aperture. Obviously, these VOC enter the plants through stomata. In case of hexanal, octanal, and (E)-3-hexenol the uptake was only limited by stomatal aperture implying that these VOC are rapidly metabolised. For nopinone the uptake seems to be limited by a slow metabolization. Estimations of deposition velocities showed that dry deposition of these compounds cannot be neglected as sink if diffusion through stomata is the limiting step for dry deposition. In such cases the lifetime with respect to dry deposiotion is comparable to the lifetime with respect to oxidation by hydroxyl radicals.

  9. Site-dependent effects of an acute intensive exercise on extracellular 5-HT and 5-HIAA levels in rat brain.

    PubMed

    Gomez-Merino, D; Béquet, F; Berthelot, M; Chennaoui, M; Guezennec, C Y

    2001-03-30

    Previous neurochemical studies have reported different pattern of 5-HT release during exercise varying across either exercise conditions or forebrain sites. This in vivo microdialysis study is the first to examine the impact of an acute intensive treadmill running (2 h at 25 m.min(-1), which is close to exhaustion time), on extracellular 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in two different brain areas in rats, the ventral hippocampus and the frontal cortex. Hippocampal and cortical 5-HT levels increased significantly after 90 min of exercise and were maximal in the first 30 min of recovery. Thereafter, cortical 5-HT levels followed a rapid and significant decrease when hippocampal levels are still maximal. During exercise, changes in extracellular 5-HIAA levels paralleled 5-HT changes, but showed no difference between the two brain areas during recovery. Thus, an intensive exercise induces a delayed increase in brain 5-HT release but recovery seems to display site-dependent patterns. PMID:11248443

  10. NOTE: The specific uptake size index for quantifying radiopharmaceutical uptake

    NASA Astrophysics Data System (ADS)

    Fleming, John S.; Bolt, Livia; Stratford, Jennifer S.; Kemp, Paul M.

    2004-07-01

    Quantitative indices of radionuclide uptake in an object of interest provide a useful adjunct to qualitative interpretation in the diagnostic application of radionuclide imaging. This note describes a new measure of total uptake of an organ, the specific uptake size index (SUSI). It can either be related in absolute terms to the total activity injected or to the specific activity in a reference region. As it depends on the total activity in the object, the value obtained will not depend on the resolution of the imaging process, as is the case with some other similar quantitative indices. This has been demonstrated in an experiment using simulated images. The application of the index to quantification of dopamine receptor SPECT imaging and parathyroid thyroid subtraction planar scintigraphy is described. The index is considered to be of potential value in reducing variation in quantitative assessment of uptake in objects with applications in all areas of radionuclide imaging.

  11. Light dependence of selenium uptake by phytoplankton and implications for predicting selenium incorporation into food webs

    USGS Publications Warehouse

    Baines, S.B.; Fisher, N.S.; Doblin, M.A.; Cutter, G.A.; Cutter, L.S.; Cole, B.

    2004-01-01

    The potentially toxic element selenium is first concentrated from solution to a large but highly variable degree by algae and bacteria before being passed on to consumers. The large loads of abiotic and detrital suspended particles often present in rivers and estuaries may obscure spatial and temporal patterns in Se concentrations at the base of the food web. We used radiotracers to estimate uptake of both selenite (Se(IV)) and C by intact plankton communities at two sites in the Sacramento/San Joaquin River Delta. Our goals were to determine (1) whether C and Se(IV) uptake were coupled, (2) the role of bacteria in Se(IV) uptake, and (3) the Se:C uptake ratio of newly produced organic material. Se(IV) uptake, like C uptake, was strongly related to irradiance. The shapes of both relationships were very similar except that at least 42-56% of Se(IV) uptake occurred in the dark, whereas C uptake in the dark was negligible. Of this dark Se(IV) uptake, 34-67% occurred in the 0.2-1.0-??m size fraction, indicating significant uptake by bacteria. In addition to dark uptake, total Se(IV) uptake consisted of a light-driven component that was in fixed proportion to C uptake. Our estimates of daily areal Se(IV):C uptake ratios agreed very well with particulate Se:C measured at a site dominated by phytoplankton biomass. Estimates of bacterial Se:C were 2.4-13 times higher than for the phytoplankton, suggesting that bacteriovores may be exposed to higher dietary Se concentrations than herbivores.

  12. Manganese uptake of imprinted polymers

    DOE Data Explorer

    Susanna Ventura

    2015-09-30

    Batch tests of manganese imprinted polymers of variable composition to assess their ability to extract lithium and manganese from synthetic brines at T=45C . Data on manganese uptake for two consecutive cycles are included.

  13. Rubidium (Potassium) Uptake by Arabidopsis

    PubMed Central

    Polley, L. David; Hopkins, Johns W.

    1979-01-01

    Experiments are reported in which the uptake of 86Rb+, used as an analog of K+, into cultured cells of Arabidopsis thaliana is investigated. A single transport system is found with Km = 0.34 millimolar and Vmax = 14 nmoles per milligram of protein per hour. This system is blocked by the metabolic inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and by cold. At high concentrations of external K+ (above 1 millimolar), a significant fraction of total uptake is energy-independent. No evidence is found for more than one energy-dependent uptake system or for concentration-dependent modifications of a carrier as postulated in multiphasic transport models. Rb+ uptake was also examined in cultured cells derived from an “osmotic mutant” of Arabidopsis. The system closely resembles that found in wild type cells with the exception that the Michaelis-Menten constants are higher: Km = 1 millimolar and Vmax = 32 nanomoles per milligram of protein per hour. The possibility that these results are artifacts associated with use of cultured cells was checked by examining 86Rb+ uptake by roots of intact seedlings of wild type Arabidopsis. A single energy-dependent transport system is found with Km = 0.42 millimolar which is not significantly different from the Km of cultured cells. There is also energy-independent uptake at high external ion concentration. PMID:16660969

  14. Uptake of {sup 64}Cu-oxine by marine phytoplankton

    SciTech Connect

    Croot, P.L.; Karson, B.; Elteren, J.T. van; Kroon, J.J.

    1999-10-15

    Short-term uptake experiments using fie phytoplankton species (Synechococcus clone DC2, Amphidinium carterae, Chrysochromulina polylepis, Ditylum brightwelli, and Prorocentrum micans) demonstrated rapid uptake of the lipophilic complex {sup 64}Cu-oxine, presumably by diffusion of the complex across the plasma membrane. This passive uptake mechanism was extremely rapid and significantly faster than facilitated uptake by the free metal ion. Measured values of the observed permeability, P{sub obs}, ranged from 0.55 to 18.6 x 10{sup {minus}4} cm s{sup {minus}1}, showing only small differences between the various algal species. Removal rate constants, k{sup bio}, varied much more widely, 0.009--570 x 10{sup {minus}9} L cell{sup {minus}1} h{sup {minus} 1}, between the algae, indicating the influence of surface area on the uptake kinetics. Maximum internal Cu levels were reached after approximately 2 h, showing that a major limiting factor in the uptake of Cu from Cu-oxine is the concentration of intracellular Cu binding sites.

  15. Uptake of antibiotics by human polymorphonuclear leukocyte cytoplasts

    SciTech Connect

    Hand, W.L.; King-Thompson, N.L. , Decatur, GA )

    1990-06-01

    Enucleated human polymorphonuclear leukocytes (PMN cytoplasts), which have no nuclei and only a few granules, retain many of the functions of intact neutrophils. To better define the mechanisms and intracellular sites of antimicrobial agent accumulation in human neutrophils, we studied the antibiotic uptake process in PMN cytoplasts. Entry of eight radiolabeled antibiotics into PMN cytoplasts was determined by means of a velocity gradient centrifugation technique. Uptakes of these antibiotics by cytoplasts were compared with our findings in intact PMN. Penicillin entered both intact PMN and cytoplasts poorly. Metronidazole achieved a concentration in cytoplasts (and PMN) equal to or somewhat less than the extracellular concentration. Chloramphenicol, a lipid-soluble drug, and trimethoprim were concentrated three- to fourfold by cytoplasts. An unusual finding was that trimethroprim, unlike other tested antibiotics, was accumulated by cytoplasts more readily at 25 degrees C than at 37 degrees C. After an initial rapid association with cytoplasts, cell-associated imipenem declined progressively with time. Clindamycin and two macrolide antibiotics (roxithromycin, erythromycin) were concentrated 7- to 14-fold by cytoplasts. This indicates that cytoplasmic granules are not essential for accumulation of these drugs. Adenosine inhibited cytoplast uptake of clindamycin, which enters intact phagocytic cells by the membrane nucleoside transport system. Roxithromycin uptake by cytoplasts was inhibited by phagocytosis, which may reduce the number of cell membrane sites available for the transport of macrolides. These studies have added to our understanding of uptake mechanisms for antibiotics which are highly concentrated in phagocytes.

  16. The MDP skull uptake test: A new diagnostic tool

    SciTech Connect

    Ell, P.J.; Jarritt, P.H.; Cullum, I.; Lui, D.

    1984-01-01

    An original approach to the measurement of bone turnover is presented. With SPECT, the authors have measured in pgr/ml, the uptake of MDP by the skull in man. The Cleon 710 scanner, ring phantoms and bone biopsies were used for ultimate in vivo/in vitro count recovery correlation and calibration. A normal range for 24 patients was found: 8.5 to 19.5 pgr/ml with a mean of 14. For patients with bony metastases (12), the values were: 22.5 to 50, mean of 30. For 5 patients with osteomalacia, the values were 46 to 68, mean of 62: for 12 patients with hyperparathyroidism, the values were 37 to 48.5, mean of 43. In 3 patients with Pagets disease, the values were 58.5 to 75, with a mean of 65. In 76 patients with metastatic disease to bone, the conventional wholebody bone scan was investigated against the following: 24h wholebody retention of MDP (WBR), skull uptake as described and GFR by Cr-51-DTPA. There is a correlation between GFR and WBR - r=0.67. There is a lesser correlation between GFR and skull uptake - r=0.3. There is no correlation between skull uptake and WBR - r=0.1. The comparison of skull uptake data with normal whole body bone scans leads to a significant proportion of cancer patients with positive skull uptake data. Monostotic disease (especially if metabolic in nature) expresses itself by abnormal skull uptake even if the clinical site of abnormality lies outside the skull. This new technique is ideal as a tool to investigate phosphonate concentration in bone. With it, the authors have shown the effect of specific activity of label on skull uptake, which increases as the specific activity of labelled MDP decreases.

  17. Uptake of I-131 MIBG by medullary thyroid cancer

    SciTech Connect

    Endo, K.; Koizumi, M.; Sakahara, H.; Nakashima, T.; Ohta, H.; Kasagi, K.; Konishi, J.; Miyauchi, A.; Kuma, K.; Torizuka, K.

    1985-05-01

    I-131 MIBG scans are useful for the localization of pheochromocytoma and neuroblastoma with high catecholamine levels. Recently the authors have found that medullary thyroid cancer also showed an uptake of I-131 MIBG in both primary neck tumors and metastatic sites. Up to now scintigraphic studies were performed in 5 patients with medullary thyroid cancer. Scintigraphy was done at 24 and 48 hours after the administration of 0.5 mCi of I-131 MIBG, thyroid uptake of dissociated I-131 being prevented by Lugol's solution. Four out of 5 cases were familial type and uptake of I-131 MIBG was similarly observed in medullary thyroid cancer as well as in pheochromocytoma. Bone metastasis of medullary thyroid cancer was also detected with I-131 MIBG. However, one case of sporadic form was negative with I-131 MIBG, whereas there was a high uptake of Tc(V)-99m dimercaptosuccinic acid: a newly developed radiopharmaceutical for medullary thyroid cancer, visualizing a different uptake mechanism of both reagents (J Nucl Med 25: 323-325, 1984). After adrenalectomy high uptake of I-131 MIBG was still observed in medullary thyroid cancer, in spite of normal catecholamine levels. The tumor to blood ratio was estimated in vivo to be about several hundreds at 24 hours after the administration. These cells are of neural crest origin and the mechanism of uptake of I-131 MIBG may not be related to the catechamine uptake mechanism. This paper concludes that I-131 MIBG is useful not only for the localization but also for the treatment of medullary thyroid cancer, as preliminary performed in pheochromocytoma and neuroblastoma.

  18. Mechanisms of Ocean Heat Uptake

    NASA Astrophysics Data System (ADS)

    Garuba, Oluwayemi

    An important parameter for the climate response to increased greenhouse gases or other radiative forcing is the speed at which heat anomalies propagate downward in the ocean. Ocean heat uptake occurs through passive advection/diffusion of surface heat anomalies and through the redistribution of existing temperature gradients due to circulation changes. Atlantic meridional overturning circulation (AMOC) weakens in a warming climate and this should slow the downward heat advection (compared to a case in which the circulation is unchanged). However, weakening AMOC also causes a deep warming through the redistributive effect, thus increasing the downward rate of heat propagation compared to unchanging circulation. Total heat uptake depends on the combined effect of these two mechanisms. Passive tracers in a perturbed CO2 quadrupling experiments are used to investigate the effect of passive advection and redistribution of temperature anomalies. A new passive tracer formulation is used to separate ocean heat uptake into contributions due to redistribution and passive advection-diffusion of surface heating during an ocean model experiment with abrupt increase in surface temperature. The spatial pattern and mechanisms of each component are examined. With further experiments, the effects of surface wind, salinity and temperature changes in changing circulation and the resulting effect on redistribution in the individual basins are isolated. Analysis of the passive advection and propagation path of the tracer show that the Southern ocean dominates heat uptake, largely through vertical and horizontal diffusion. Vertical diffusion transports the tracer across isopycnals down to about 1000m in 100 years in the Southern ocean. Advection is more important in the subtropical cells and in the Atlantic high latitudes, both with a short time scale of about 20 years. The shallow subtropical cells transport the tracer down to about 500m along isopycnal surfaces, below this vertical

  19. Nitrogen Uptake in Spinach

    NASA Astrophysics Data System (ADS)

    Ramirez, J.; VanBenthem, P.

    2013-12-01

    A plant's absorption of nitrogen can be encouraged by a variety of environmental factors, especially the application of fertilizers. As a common limiting factor in plant growth, not up taking enough nitrogen can be a result of an unhealthy plant. Moreover, as farmers seek out methods to increase growth of plants, fertilizers are used as a solution to the issue of nitrogen deficiency to incorporate additional nitrogen from chemical or organic sources, by not using the right fertilizer can greatly affect the plats. The point of this research project is to determine the effect of various fertilizers on the plant growth, and to correlate the measured nitrogen, water and chlorophyll content in spinach leaves. Spinach leaves were used because they are known to quickly uptake chemicals in the environment. The spinach plants were exposed to four different growing parameters, which are referred to as control, ammonium nitrate, MiracleGro , and organic. The spinach was originally placed in nitrogen deficient soil with only 2.2x10 4 weight percent (wt. %) nitrogen. The leaves in the control group were grown in this nitrogen deficient soil without any fertilizer added. Ammomium nitrate and MiracleGro were added to the spinach in the A and MG groups, respectively, and organic chicken stool was used for the O group. By using a spectral imaging system and flame combustion techniques, the chlorophyll content can be related to the nitrogen content in the spinach leaves. In these spinach leaves, nitrogen and chlorophyll content were measured, chlorophyll is a green pigment that plays a crucial role in producing nutrients for green plants. The lack of chlorophyll will allow the plant to become susceptible to diseases, so it is extremely important that the plants have a high content of chlorophyll. The role of nitrogen in chlorophyll is very important and helps in the creation of chlorophyll; therefore it is necessary that an appropriate amount of nitrogen is added for optimal growth

  20. The intestinal uptake of particles and the implications for drug and antigen delivery.

    PubMed Central

    O'Hagan, D T

    1996-01-01

    A number of researchers from different scientific disciplines have independently described the uptake of a variety of particulates across the gastrointestinal tract in animal models. The reports of particle uptake are briefly reviewed and the alternative mechanisms and proposed sites of uptake are discussed. Following these observations, some researchers have exploited the phenomenon of particulate uptake by using microparticles and nanoparticles as oral delivery systems for active agents, such as drugs and vaccines. The potential use of particulate carrier systems as drug and vaccine delivery systems is also briefly discussed. PMID:8982819

  1. UPTAKE OF BROMACIL BY ISOLATED BARLEY ROOTS

    EPA Science Inventory

    A study of bromacil uptake by excised barley (Hordeum Vulgare) roots was used to evaluate this procedure as a tool to learn the uptake characteristics of toxic organic chemicals. Bromacil uptake was shown to be a passive process with an uptake rate (at 0.8 mg/l) of 0.64 microgram...

  2. Through form to function: root hair development and nutrient uptake

    NASA Technical Reports Server (NTRS)

    Gilroy, S.; Jones, D. L.

    2000-01-01

    Root hairs project from the surface of the root to aid nutrient and water uptake and to anchor the plant in the soil. Their formation involves the precise control of cell fate and localized cell growth. We are now beginning to unravel the complexities of the molecular interactions that underlie this developmental regulation. In addition, after years of speculation, nutrient transport by root hairs has been demonstrated clearly at the physiological and molecular level, with evidence for root hairs being intense sites of H(+)-ATPase activity and involved in the uptake of Ca(2+), K(+), NH(4)(+), NO(3)(-), Mn(2+), Zn(2+), Cl(-) and H(2)PO(4)(-).

  3. Pharmacological characterization of binding sites identified in rat brain following in vivo administration of [3H]-spiperone.

    PubMed Central

    Chivers, J.; Jenner, P.; Marsden, C. D.

    1987-01-01

    [3H]-spiperone is commonly used to label dopamine receptors in vitro in brain tissue. However, spiperone also interacts with brain 5-hydroxytryptamine and noradrenaline receptors. In vivo, [3H]-spiperone has been used for identifying dopamine receptors in both animals and man but the nature of the sites identified is unknown. The in vivo administration of [3H]-spiperone to rats leads to a selective accumulation of radioactivity in the olfactory lobes, tuberculum olfactorium, nucleus accumbens, striatum, substantia nigra, hippocampus, frontal cortex and hypothalamus, when compared to the cerebellum. In vivo drug displacement studies suggest that the binding of [3H]-spiperone in these areas may be to dopamine, 5-HT or noradrenaline receptors. [3H]-spiperone in vivo mainly labels dopamine receptors in striatum, tuberculum olfactorium, hypothalamus, substantia nigra and olfactory lobes. However, in the frontal cortex and nucleus accumbens specific binding involves not only dopamine receptors but also 5-HT and/or noradrenaline receptors. Interpretation of in vivo studies in man using radioactive spiperone and its derivatives must take into account the fact that this ligand only labels dopamine receptors in some brain areas. PMID:2882801

  4. Specificity of the Antibody Receptor Site to D-Lysergamide: Model of a Physiological Receptor for Lysergic Acid Diethylamide

    PubMed Central

    Vunakis, Helen Van; Farrow, John T.; Gjika, Hilda B.; Levine, Lawrence

    1971-01-01

    Antibodies to D-lysergic acid have been produced in rabbits and guinea pigs and a radioimmunoassay for the hapten was developed. The specificity of this lysergamide-antilysergamide reaction was determined by competitive binding with unlabeled lysergic acid diethylamide (LSD), psychotomimetic drugs, neurotransmitters, and other compounds with diverse structures. LSD and several related ergot alkaloids were potent competitors, three to seven times more potent than lysergic acid itself. The N,N-dimethyl derivatives of several compounds, including tryptamine, 5-hydroxytryptamine, 4-hydroxytryptamine, 5-methoxytryptamine, tyramine, and mescaline, were only about ten times less effective than lysergic acid, even though these compounds lack some of the ring systems of lysergic acid. The pattern of inhibition by related compounds with various substituents suggests that the antibody receptor site recognizes structural features resembling the LSD molecule. In particular, the aromatic nucleus and the dimethylated ethylamine side chain in phenylethylamine and tryptamine derivatives may assume in solution a conformation resembling ring A and the methylated nitrogen in ring C of LSD. Among the tryptamine derivatives, a large percentage of the most potent competitors are also psychotomimetic compounds. PMID:5283939

  5. l-Methionine Placental Uptake

    PubMed Central

    Araújo, João R.; Correia-Branco, Ana; Ramalho, Carla; Gonçalves, Pedro; Pinho, Maria J.; Keating, Elisa

    2013-01-01

    Our aim was to investigate the influence of gestational diabetes mellitus (GDM) and GDM-associated conditions upon the placental uptake of 14C-l-methionine (14C-l-Met). The 14C-l-Met uptake by human trophoblasts (TBs) obtained from normal pregnancies (normal trophoblast [NTB] cells) is mainly system l-type amino acid transporter 1 (LAT1 [L])-mediated, although a small contribution of system y+LAT2 is also present. Comparison of 14C-l-Met uptake by NTB and by human TBs obtained from GDM pregnancies (diabetic trophoblast [DTB] cells) reveals similar kinetics, but a contribution of systems A, LAT2, and b0+ and a greater contribution of system y+LAT1 appears to exist in DTB cells. Short-term exposure to insulin and long-term exposure to high glucose, tumor necrosis factor-α, and leptin decrease 14C-l-Met uptake in a human TB (Bewo) cell line. The effect of leptin was dependent upon phosphoinositide 3-kinase, extracellular-signal-regulated kinase 1/2 (ERK/MEK 1/2), and p38 mitogen-activated protein kinase. In conclusion, GDM does not quantitatively alter 14C-l-Met placental uptake, although it changes the nature of transporters involved in that process. PMID:23653387

  6. UPTAKE OF RADIONUCLIDE METALS BY SPME FIBERS

    SciTech Connect

    Duff, M; S Crump, S; Robert02 Ray, R; Keisha Martin, K; Donna Beals, D

    2006-08-28

    The Federal Bureau of Investigation (FBI) Laboratory currently does not have on site facilities for handling radioactive evidentiary materials and there are no established FBI methods or procedures for decontaminating high explosive (HE) and fire debris (FD) evidence while maintaining evidentiary value. One experimental method for the isolation of HE and FD residue involves using solid phase microextraction or SPME fibers to remove residue of interest. Due to their high affinity for organics, SPME fibers should have little affinity for most metals. However, no studies have measured the affinity of radionuclides for SPME fibers. The focus of this research was to examine the affinity of dissolved radionuclide ({sup 239/240}Pu, {sup 238}U, {sup 237}Np, {sup 85}Sr, {sup 133}Ba, {sup 137}Cs, {sup 60}Co and {sup 226}Ra) and stable radionuclide surrogate metals (Sr, Co, Ir, Re, Ni, Ba, Cs, Nb, Zr, Ru, and Nd) for SPME fibers at the exposure conditions that favor the uptake of HE and FD residues. Our results from radiochemical and mass spectrometric analyses indicate these metals have little measurable affinity for these SPME fibers during conditions that are conducive to HE and FD residue uptake with subsequent analysis by liquid or gas phase chromatography with mass spectrometric detection.

  7. Tumor uptake of radioruthenium compounds

    SciTech Connect

    Srivastava, S C; Richards, P; Meinken, G E; Larson, S M; Grunbaum, Z

    1980-01-01

    The use of ruthenium-97 as a scintigraphic agent, particularly for tumor localization, is investigated. The tumor uptake of ruthenium chloride and ruthenium-labelled transferrin is evaluated and their application as tumor-imagine agents is compared to gallium-67 citrate. (ACR)

  8. Uptake of atmospheric tritium by market foods

    SciTech Connect

    Inoue, Y.; Tanaka-Miyamoto, K.; Iwakura, T. )

    1992-03-01

    In this paper uptake of tritium by market foods from tritiated water vapor in the air is investigated using cereals and beans purchased in Deep River, Canada. The concentrations of tissue free water tritium (TFWT) and organically bound tritium (OBT) range from 12 to 79% and from 10 to 38% respectively, of that estimated for atmospheric water vapor of the sampling month. The specific activity ratios of OBT to TFWT were constant for cereals, but variable for beans. The elevated OBT was shown to be the result of isotopic exchange of labile hydrogen by the fact that washing the foods with tritium free-water reduced their tritium contents to levels characteristic of their production sites.

  9. Pulmonary uptake of morphine (M)

    SciTech Connect

    Roerig, D.L.; Bunke, S.S.; Kotrly, K.J.; Dawson, C.A.; Kampine, J.P.

    1986-03-01

    Previously the authors reported less than 5% of M was taken up during the first pass through the human lung. The low uptake of this basic lipophilic amine was further investigated in a single pass isolated perfused rat lung (IPL) in comparison to uptake of radiolabelled H/sub 2/O, antipyrine (A), aminopyrine (AM), nicotine (N) and phenylethylamine (P). The IPL was perfused for 5 min with each drug (5nmol/ml) and effluent collected in 10 sec fractions. Pulmonary extraction was calculated using indocyanine green dye as a non-extractable reference indicator. Accumulation of all compounds in the IPL reached an apparent equilibrium within 4 min. At equilibrium lung/perfusate conc. ratios for H/sub 2/O, A, AM, N, P and M were 1.04, 0.84, 0.85, 1.44, 2.57 and 1.13 respectively. The time course of M uptake differed from the other compounds since initial extraction of M was low (23%) compared to 75%, 53%, 35%, 82% and 86% for H/sub 2/O, A, AM, N and P respectively. Also, the half time to equilibrium for M was longer (50 sec) compared to 18, 21, 26, 19 and 22 sec for H/sub 2/O, A, AM, N and P respectively. The low initial pulmonary extraction of M compared to these compounds followed by greater M extraction during the remainder of drug infusion suggests uptake mechanisms for M different than the flow limited uptake for water and other basic amine drugs.

  10. Lithium isotope fractionation during uptake by gibbsite

    NASA Astrophysics Data System (ADS)

    Wimpenny, Josh; Colla, Christopher A.; Yu, Ping; Yin, Qing-Zhu; Rustad, James R.; Casey, William H.

    2015-11-01

    The intercalation of lithium from solution into the six-membered μ2-oxo rings on the basal planes of gibbsite is well-constrained chemically. The product is a lithiated layered-double hydroxide solid that forms via in situ phase change. The reaction has well established kinetics and is associated with a distinct swelling of the gibbsite as counter ions enter the interlayer to balance the charge of lithiation. Lithium reacts to fill a fixed and well identifiable crystallographic site and has no solvation waters. Our lithium-isotope data shows that 6Li is favored during this intercalation and that the solid-solution fractionation depends on temperature, electrolyte concentration and counter ion identity (whether Cl-, NO3- or ClO4-). We find that the amount of isotopic fractionation between solid and solution (ΔLisolid-solution) varies with the amount of lithium taken up into the gibbsite structure, which itself depends upon the extent of conversion and also varies with electrolyte concentration and in the counter ion in the order: ClO4- < NO3- < Cl-. Higher electrolyte concentrations cause more rapid expansion of the gibbsite interlayer and some counter ions, such as Cl-, are more easily taken up than others, probably because they ease diffusion. The relationship between lithium loading and ΔLisolid-solution indicates two stages: (1) uptake into the crystallographic sites that favors light lithium, in parallel with adsorption of solvated cations, and (2) continued uptake of solvated cations after all available octahedral vacancies are filled; this second stage has no isotopic preference. The two-step reaction progress is supported by solid-state NMR spectra that clearly resolve a second reservoir of lithium in addition to the expected layered double-hydroxide phase.

  11. Polyamine Uptake, Kinetics, and Competition among Polyamines and between Polyamines and Inorganic Cations.

    PubMed

    Pistocchi, R; Bagni, N; Creus, J A

    1986-02-01

    Polyamine uptake, the kinetics of this uptake, and the competition among polyamines and between polyamines and inorganic cations were studied in petals of Saintpaulia ionantha Wendl. Uptake experiments using (14)C-labeled polyamines were carried out on single petals, at room temperaure (20 degrees C) and in the light. The results show that putrescine, spermidine, and spermine uptake was dependent on the external pH and occurred up to high external polyamine concentrations with K(m) values of 8.6, 1.2, and 2.1 millimolar, respectively, with spermidine being the most absorbed at low concentration (17 micromolar). Putrescine and spermidine did not seem to compete for the same site of absorption. Furthermore, putrescine and spermidine uptake was not inhibited by Ca(2+), Mg(2+), and K(+) at the same concentrations (17 micromolar), whereas 1.7 millimolar Ca(2+) inhibited and K(+) enhanced spermidine uptake. The intracellular localization of the absorbed putrescine was determined using two different methods. Very little label was found in the apoplast, while most of it was localized in the 98,500g supernatant. According to our data the vacuole, which represents a substantial part of Saintpaulia parenchyma cells, could be a site of putrescine accumulation. 2,4-Dinitrophenol and diethylstilbestrol did not inhibit uptake; however, at 0 degrees C there was a 35% inhibition of spermidine uptake, compared with the controls kept at 20 degrees C as well as a 68% inhibition with 20 millimolar NaSCN. PMID:16664661

  12. Uptake of auxins into membrane vesicles isolated from pea stems: an in vitro auxin transport system

    SciTech Connect

    Slone, J.H.

    1985-01-01

    The objective of this research was to test the applicability of the chemiosmotic theory of auxin transport to a subcellular system. Membrane vesicles were isolated from the basal portion of the third internode of etiolated pea plants (Pisum sativum L. var. Alaska) by differential centrifugation. Uptake of auxin was determined by adding /sup 14/C-labeled indoleacetic acid (IAA) to vesicles. Nigericin, a monovalent cation ionophore, and the electrogenic protonophore, carbonyl-cyanide m-chlorophenylhydrazone (CCCP), at micromolar concentrations abolished saturable uptake. Bursting vesicles by sonication, osmotic shock and freeze/thawing also eliminated saturable uptake. As the temperature increased from 0 to 30/sup 0/C, saturable uptake decreased markedly. Nonsaturable auxin uptake was less affected by these treatments. The pH gradient-dependent uptake of auxin appeared to be a transmembrane uptake of auxin into the vesicles rather than surface binding. Unlabeled IAA, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-naphthaleneacetic acid (NAA) at low concentrations reduced the saturable accumulation of (/sup 14/C)IAA in vesicles, while phenylacetic acid, benzoic acid, and 1-NAA were effective only at high concentrations. Kinetic analysis revealed two types of sites: a high affinity site with an uptake capacity of 25 to 40 pmoles/g tissue, and a low affinity site with an uptake capacity of 260 to 600 pmole/g tissue, fresh wt. In conclusion, several principal elements of an auxin transport system, as specific by the chemiosmotic theory of polar auxin transport, were present in membrane vesicles isolated from relatively mature pea stem tissue. However, one important aspect of the theory was not demonstrated in this in vitro system - a TIBA/NPA-sensitive auxin efflux. The kinetics and specificity of auxin uptake strongly suggested that this system was physiologically significant.

  13. Anorectic activities of serotonin uptake inhibitors: correlation with their potencies at inhibiting serotonin uptake in vivo and /sup 3/H-mazindol binding in vitro

    SciTech Connect

    Angel, I.; Taranger, M.A.; Claustre, Y.; Scatton, B.; Langer, S.Z.

    1988-01-01

    The mechanism of anorectic action of several serotonin uptake inhibitors was investigated by comparing their anorectic potencies with several biochemical and pharmacological properties and in reference to the novel compound SL 81.0385. The anorectic effect of the potent serotonin uptake inhibitor SL 81.0385 was potentiated by pretreatment with 5-hydroxytryptophan and blocked by the serotonin receptor antagonist metergoline. A good correlation was obtained between the ED/sub 50/ values of anorectic action and the ED/sub 50/ values of serotonin uptake inhibition in vivo (but not in vitro) for several specific serotonin uptake inhibitors. Most of the drugs tested displaced (/sup 3/H)-mazindol from its binding to the anorectic recognition site in the hypothalamus, except the pro-drug zimelidine which was inactive. Excluding zimelidine, a good correlation was obtained between the affinities of these drugs for (/sup 3/H)-mazindol binding and their anorectic action indicating that their anorectic activity may be associated with an effect mediated through this site. Taken together these results suggest that the anorectic action of serotonin uptake inhibitors is directly associated to their ability to inhibit serotonin uptake and thus increasing the synaptic levels of serotonin. The interactions of these drugs with the anorectic recognition site labelled with (/sup 3/H)-mazindol is discussed in connection with the serotonergic regulation of carbohydrate intake.

  14. Phosphate uptake kinetics by Acinetobacter isolates.

    PubMed

    Pauli, A S; Kaitala, S

    1997-02-01

    Acinetobacter isolates from activated sludge treatment plants of forest industry were used as model organisms for polyphosphate accumulating bacteria to study excess phosphate uptake by the overplus phenomenon as well as luxury uptake of phosphate during growth. The initial, rapid phosphate uptake by the phosphorus-starved Acinetobacter isolates (the overplus phenomenon) followed the Michaelis-Menten model (maximum initial phosphate uptake rate 29 mg P g(-1) dry mass (DM) h(-1), half-saturation constant for excess phosphate uptake 17 mg P L(-1)). During the rapid uptake no growth was observed, but most cells contained polyphosphate granules. Also growth and luxury uptake of phosphate could be modeled with the Michaelis-Menten equation (maximum phosphate uptake rate 3.7-12 mg P g(-1) DM h(-1), half-saturation constant for growth 0.47-6.0 mg P L(-1), maximum specific growth rate 0.15-0.55 h(-1)). PMID:18633985

  15. A molecular recognizing system of serotonin in rat fetal axonal growth cones: uptake and high affinity binding.

    PubMed

    Mercado, R; Hernández, J

    1992-09-18

    Axonal growth cone particles (AGCP) isolated from prenatal and postnatal rat brain had different high-affinity 5-HT uptake characteristics. In postnatal AGCP the uptake behaves as in the adult rat brain, while in the prenatal AGCP the uptake characteristics seem to be in a transitional stage. Also in prenatal AGCP we observed specific, high-affinity 5-HT binding sites. These results support the idea of an important role for 5-HT during axogenesis. PMID:1424085

  16. Cellular uptake of metallated cobalamins.

    PubMed

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry; Gammelgaard, Bente; Furger, Evelyne; Alberto, Roger

    2016-03-16

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-) and H2O, respectively), were included as control samples. The results indicated that B12 derivatives delivered cisplatin to both cellular cytosol and nuclei with an efficiency of one third compared to the uptake of free cisplatin cis-[Pt(II)Cl2(NH3)2]. In addition, uptake of charged B12 derivatives including [Cbl-OH2](+), [{Co}-CN-{cis-PtCl(NH3)2}](+), [{Re}-{Co}-CN-{cis-PtCl(NH3)2}](+), and [{Co}-CN-{trans-Pt(Cyt)(NH3)2}](2+) (Cyt = cytarabin) was high compared to neutral B12, which implied the existence of an additional internalization pathway for charged B12 vitamin analogs. The affinities of the charged B12 derivatives to the B12 transporters HC, IF and TC were similar to that of native vitamin B12. PMID:26739575

  17. Improving vaccine uptake: An overview

    PubMed Central

    Falconer, Michelle Anne

    2013-01-01

    A task group was formed with the aim to improve the quality of the service offered by ensuring that all children waiting for an appointment for vaccination would be offered one at the earliest opportunity. Children aged between 12 mo–5 y that were not completely immunized for their age were identified and included in a pilot catch-up session. Following evaluation of the pilot session, four further immunization sessions were delivered. A total of 398 children attended the four sessions, representing an improved attendance rate of 39%. Most parents brought their children between 11am–3pm and 728 vaccines were administered: 339 MMR; 255 Pre-school boosters; 53 Hib/MenC and 81 PCV. Uptake of MMR vaccine in the PCT at age 24 mo increased by 9% by Q3 2008. For children aged five years, uptake of the first dose of MMR vaccine increased from 91.9% to 94% for the first dose and from 82.3 to 82.5% for the second dose by Q3 2008. This project demonstrates that new ways of delivering immunization sessions can be successfully implemented which can enhance access through the use of alternative venues and subsequently lead to increased vaccine uptake. PMID:23732890

  18. Site Partition: Turning One Site into Two for Adsorbing CO2.

    PubMed

    Tian, Ziqi; Dai, Sheng; Jiang, De-En

    2016-07-01

    We propose the concept of site partition to explain the role of guest molecules in increasing CO2 uptake in metal-organic frameworks and to design new covalent porous materials for CO2 capture. From grand canonical Monte Carlo simulations of CO2 sorption in the recently synthesized CPM-33 MOFs, we show that guest insertion divides one open metal site into two relatively strong binding sites, hence dramatically increasing CO2 uptake. Further, we extend the site partition concept to covalent organic frameworks with large free volume. After insertion of a designed geometry-matching guest, we show that the volumetric uptake of CO2 doubles. Therefore, the concept of site partition can be used to engineer the pore space of nanoporous materials for higher gas uptake. PMID:27320252

  19. Macroscopic modeling of plant water uptake: soil and root resistances

    NASA Astrophysics Data System (ADS)

    Vogel, Tomas; Votrubova, Jana; Dohnal, Michal; Dusek, Jaromir

    2014-05-01

    The macroscopic physically-based plant root water uptake (RWU) model, based on water-potential-gradient formulation (Vogel et al., 2013), was used to simulate the observed soil-plant-atmosphere interactions at a forest site located in a temperate humid climate of central Europe and to gain an improved insight into the mutual interplay of RWU parameters that affects the soil water distribution in the root zone. In the applied RWU model, the uptake rates are directly proportional to the potential gradient and indirectly proportional to the local soil and root resistances to water flow. The RWU algorithm is implemented in a one-dimensional dual-continuum model of soil water flow based on Richards' equation. The RWU model is defined by four parameters (root length density distribution, average active root radius, radial root resistance, and the threshold value of the root xylem potential). In addition, soil resistance to water extraction by roots is related to soil hydraulic conductivity function and actual soil water content. The RWU model is capable of simulating both the compensatory root water uptake, in situations when reduced uptake from dry layers is compensated by increased uptake from wetter layers, and the root-mediated hydraulic redistribution of soil water, contributing to more natural soil moisture distribution throughout the root zone. The present study focusses on the sensitivity analysis of the combined soil water flow and RWU model responses in respect to variations of RWU model parameters. Vogel T., M. Dohnal, J. Dusek, J. Votrubova, and M. Tesar. 2013. Macroscopic modeling of plant water uptake in a forest stand involving root-mediated soil-water redistribution. Vadose Zone Journal, 12, 10.2136/vzj2012.0154.

  20. Detecting spatio-temporal controls on depth distributions of root water uptake using soil moisture patterns

    NASA Astrophysics Data System (ADS)

    Blume, Theresa; Heidbüchel, Ingo; Simard, Sonia; Güntner, Andreas; Weiler, Markus

    2016-04-01

    Landscape scale soil moisture patterns show a pronounced shift when plants become active during the growing season. Soil moisture patterns are then not only controlled by soils, topography and related abiotic site characteristics as well as site characteristic throughfall patterns but also by root water uptake. In this study root water uptake from different soil depths is estimated based on diurnal fluctuations in soil moisture content and was investigated with a setup of 15 field sites in a forest in northeastern Germany. These sites cover different topographic positions and forest stands. Vegetation types include pine forest (young and old) and different deciduous forest stands. Available data at all sites includes information at high temporal resolution from 5 soil moisture and soil temperature profiles, matric potential, piezometers and sapflow sensors as well as standard climate data. The resulting comprehensive data set of depth distributed root water uptake shows differences in overall amounts as well as in uptake depth distributions between different forest stands, but also related to slope position and thus depth to groundwater. Temporal dynamics of signal strength within the profile suggest a locally shifting spatial distribution of root water uptake depending on water availability. The relative contributions of the different depths to overall root water uptake shift as the summer progresses. However, the relationship of these depth resolved uptake rates to overall soil water availability varies considerably between tree species. This unique data set of depth specific contributions to root water uptake down to a depth of 2 m allows a much more detailed analysis of tree response to water availability than the more common transpiration estimates generated by sapflow or eddy flux measurements.

  1. The uptake of cardiac glycosides in relation to their actions in isolated cardiac muscle

    PubMed Central

    Godfraind, T.; Lesne, M.

    1972-01-01

    1. The uptake of 3H-digitoxin, 3H-ouabain and 3H-dihydro-ouabain by isolated guinea-pig atria has been studied and compared with the inhibition of the sodium pump and with the inotropic effect. 2. Analysis of the curve relating the uptake of digitoxin and ouabain at equilibrium to the bath concentration enabled a non-saturable and a saturable binding site to be distinguished. 3. The uptake of inactive doses of dihydro-ouabain was only by a non-saturable mechanism. 4. The uptake of labelled digitoxin and ouabain was reduced in the presence of another glycoside. The amount of bound glycoside was nearly equivalent to the estimated non-saturable uptake. 5. The uptake was reduced at 4° C to the clearance of the non-saturable site. 6. ED50 of digitoxin and of ouabain for inhibition of the sodium pump were measured and compared to the ED50 for inotropic effect and to the concentrations producing a half-saturation of the saturable binding site. 7. It is concluded that binding to the saturable site may be responsible for the cardiac actions of the glycosides. PMID:4656610

  2. Bisphosphonate Uptake in Areas of Tooth Extraction or Periapical Disease

    PubMed Central

    Cheong, Simon; Sun, Shuting; Kang, Benjamin; Bezouglaia, Olga; Elashoff, David; McKenna, Charles E.; Aghaloo, Tara L.; Tetradis, Sotirios

    2015-01-01

    Purpose Bisphosphonates (BPs) are widely used for the management of bone diseases such as osteoporosis and bone malignancy. However, osteonecrosis of the jaws (ONJ) is a serious complication of BP treatment. ONJ lesions mainly occur after extraction of teeth deemed unrestorable or around teeth with active periodontal or periapical disease. Because socket healing or dental disease shows higher bone turnover, the authors hypothesized that preferentially high BP accumulation would be observed in these areas. Materials and Methods The authors tested the uptake of fluorescein-labeled zoledronic acid (5-FAM-ZOL) in sites of tooth extraction or experimental periapical disease in mice. Maxillary molars were extracted or the crowns of mandibular molars were drilled to induce pulp exposure. Animals were injected with 5-FAM-ZOL 200 μg/kg at various times after intervention and fluorescence was measured at healthy versus intervention sites. Fluorescein injections were used as controls. Data were analyzed by t test and mixed effects linear models were constructed because the animals had repeated measurements over time and at the 2 sites. Results A statistically significant (P ≤ .001 to .002) time-dependent uptake of 5-FAM-ZOL was detected in the areas of extraction socket and in the alveolar ridge around teeth with periapical disease compared with the healthy contralateral sites of the same animals. For the 2 conditions, the uptake reached a maximum 3 days after experimental intervention and decreased thereafter. Conclusions These data suggest that sites with increased bone turnover, such as extraction sites or areas of periapical inflammation, are exposed to higher BP doses than the remaining alveolar ridge and could explain, at least in part, the susceptibility of such areas to ONJ. PMID:25262401

  3. Field and Laboratory Measurements of H2 Uptake by Soils Designed to Yield Parameters for a Global Model

    NASA Astrophysics Data System (ADS)

    Downey, N. V.; Randerson, J. T.; Eiler, J. M.

    2005-12-01

    Soil uptake of molecular hydrogen (H2) is the dominant loss term for atmospheric H2, but the distribution and magnitude of this global sink are not well known. We combined field and laboratory experiments to estimate the sensitivity of H2 fluxes to temperature and soil moisture controls. H2 uptake by soils was measured at three sites in California for one year. Our sites included forest, desert and marsh ecosystems. Uptake rates, vertical profiles of soil H2 concentrations, soil temperature, soil moisture and CO2 fluxes were measured at each site. H2 uptake rates ranged from 0 to 23 nmol/m2/s. CO2 fluxes and H2 fluxes did not correlate at our field sites. Soil moisture was positively correlated with H2 uptake rate in the desert ecosystem. Soil samples were returned to the lab, where uptake rates as a function of temperature and soil moisture were measured with a flow through system. We observed a strong temperature dependence of uptake rate in laboratory experiments for temperatures ranging from -20 ° C to 60 ° C. H2 uptake reached a maximum at 37 ° C and persisted to temperatures below -10 ° C. Between 0 ° C and 20 ° C H2 fluxes increased by 350%. These results were used to develop a global model of the soil H2 sink.

  4. Root Water Uptake and Soil Moisture Pattern Dynamics - Capturing Connections, Controls and Causalities

    NASA Astrophysics Data System (ADS)

    Blume, T.; Heidbuechel, I.; Hassler, S. K.; Simard, S.; Guntner, A.; Stewart, R. D.; Weiler, M.

    2015-12-01

    We hypothesize that there is a shift in controls on landscape scale soil moisture patterns when plants become active during the growing season. Especially during the summer soil moisture patterns are not only controlled by soils, topography and related abiotic site characteristics but also by root water uptake. Root water uptake influences soil moisture patterns both in the lateral and vertical direction. Plant water uptake from different soil depths is estimated based on diurnal fluctuations in soil moisture content and was investigated with a unique setup of 46 field sites in Luxemburg and 15 field sites in Germany. These sites cover a range of geologies, soils, topographic positions and types of vegetation. Vegetation types include pasture, pine forest (young and old) and different deciduous forest stands. Available data at all sites includes information at high temporal resolution from 3-5 soil moisture and soil temperature profiles, matrix potential, piezometers and sapflow sensors as well as standard climate data. At sites with access to a stream, discharge or water level is also recorded. The analysis of soil moisture patterns over time indicates a shift in regime depending on season. Depth profiles of root water uptake show strong differences between different forest stands, with maximum depths ranging between 50 and 200 cm. Temporal dynamics of signal strength within the profile furthermore suggest a locally shifting spatial distribution of root water uptake depending on water availability. We will investigate temporal thresholds (under which conditions spatial patterns of root water uptake become most distinct) as well as landscape controls on soil moisture and root water uptake dynamics.

  5. A microfluidic method for dopamine uptake measurements in dopaminergic neurons.

    PubMed

    Yu, Yue; Shamsi, Mohtashim H; Krastev, Dimitar L; Dryden, Michael D M; Leung, Yen; Wheeler, Aaron R

    2016-02-01

    Dopamine (DA) is a classical neurotransmitter and dysfunction in its synaptic handling underlies many neurological disorders, including addiction, depression, and neurodegeneration. A key to understanding DA dysfunction is the accurate measurement of dopamine uptake by dopaminergic neurons. Current methods that allow for the analysis of dopamine uptake rely on standard multiwell-plate based ELISA, or on carbon-fibre microelectrodes used in in vivo recording techniques. The former suffers from challenges associated with automation and analyte degradation, while the latter has low throughput and is not ideal for laboratory screening. In response to these challenges, we introduce a digital microfluidic platform to evaluate dopamine homeostasis in in vitro neuron culture. The method features voltammetric dopamine sensors with limit of detection of 30 nM integrated with cell culture sites for multi-day neuron culture and differentiation. We demonstrate the utility of the new technique for DA uptake assays featuring in-line culture and analysis, with a determination of uptake of approximately ∼32 fmol in 10 min per virtual microwell (each containing ∼200 differentiated SH-SY5Y cells). We propose that future generations of this technique will be useful for drug discovery for neurodegenerative disease as well as for a wide range of applications that would benefit from integrated cell culture and electroanalysis. PMID:26725686

  6. A mechanism for the hydrogen uptake process in zirconium alloys

    NASA Astrophysics Data System (ADS)

    Cox, B.

    1999-01-01

    Hydrogen uptake data for thin Zircaloy-2 specimens in steam at 300-400°C have been analysed to show that there is a decrease in the rate of uptake with respect to the rate of oxidation when the terminal solid solubility (TSS) of hydrogen in the metal is exceeded. In order for TSS to be reached during pre-transition oxidation a very thin 0.125 mm Zircaloy sheet was used. The specimens had been pickled initially removing all Zr 2(Fe/Ni) particles from the initial surfaces, yet the initial hydrogen uptake rates were still much higher than for Zircaloy-4 or a binary Zr/Fe alloy that did not contain phases that dissolve readily during pickling. Cathodic polarisation at room temperature in CuSO 4 solution showed that small cracks or pores formed the cathodic sites in pre-transition oxide films. Some were at pits resulting from the initial dissolution of the Zr 2(Fe/Ni) phase; others were not; none were at the remaining intermetallics in the original surface. These small cracks are thought to provide the ingress routes for hydrogen. A microscopic steam starvation process at the bottoms of these small cracks or pores, leading to the accumulation of hydrogen adjacent to the oxide/metal interface, and causing breakdown of the passive oxide forming at the bottom of the flaw, is thought to provide the mechanism for the hydrogen uptake process during both pre-transition and post-transition oxidation.

  7. DNA UPTAKE BY TRANSFORMABLE BACTERIA

    SciTech Connect

    LACKS,S.A.

    1999-09-07

    The various processes of DNA uptake by cells can be categorized as: viral DNA entry, conjugation, or transformation. Within each category, a variety of mechanisms have been found. However, considerable similarities occur among the different mechanisms of conjugation and, especially, transformation. All of these natural mechanisms of DNA transfer are quite elaborate and involve multiple protein components, as the case may be, of the virus, the donor cell, and the recipient cell. The mechanisms of viral infection and conjugation will be discussed mainly with respect to their relevance to transformation.

  8. DNA Uptake by Transformable Bacteria

    SciTech Connect

    Lacks, Sanford A.

    1999-03-31

    The various processes of DNA uptake by cells can be categorized as: viral DNA entry, conjugation, or transformation. Within each category, a variety of mechanisms have been found. However, considerable similarities occur among the different mechanisms of conjugation and, especially, transformation. All of these natural mechanisms of DNA transfer are quite elaborate and involve multiple protein components, as the case may be, of the virus, the donor cell, and the recipient cell. The mechanisms of viral infection and conjugation will be discussed mainly with respect to their relevance to transformation.

  9. Continuous In-Stream Assimilatory Nitrate Uptake from High Frequency Sensor Measurements

    NASA Astrophysics Data System (ADS)

    Rode, Michael; Rehan Anis, Muhammad; Weitere, Markus

    2016-04-01

    Recently developed in situ sensors provide new opportunities to measure changes in stream concentration at high temporal frequencies that historical have not been feasible. In this study we used multi-parameter sensor measurements to relate assimilatory uptake to metabolic rates and calculate continually uptake rates for two stream reaches and a whole stream network. Two years of continues 15 min data from a forest and agricultural stream reach of the Selke river (463km2) revealed strong correlation between assimilatory uptake and GPP for the forest (r2=0.72) and agricultural (r2=0.56) stream reach. The slopes of these regressions were in good agreement with predicted assimilatory N-uptake based on additional metabolism data. Mean yearly assimilatory uptake rates were 6.4 times higher in the agricultural stream (mean 68.5 mgNm‑2d‑1, max 270 mgNm‑2d‑1) than in the forest stream (mean 10.7 mgNm‑2d‑1, max 97.5 mgNm‑2d‑1). Percentage daily assimilatory uptake amounted up to 47.4 % in the whole mainly agricultural watershed, whereas the total yearly assimilatory in-stream uptake was 9.0% of total nitrogen load of the watershed. This value was lower in the forest dominated upstream watershed (4.8%) and higher in the lower agriculture dominated watershed (13.4%). High frequency measurements offer exploring continues nutrient uptake metrics for streams with strongly deviating site characteristics.

  10. Organic and inorganic nitrogen uptake in lichens.

    PubMed

    Dahlman, Lena; Persson, Jörgen; Palmqvist, Kristin; Näsholm, Torgny

    2004-07-01

    In order to learn more about nitrogen (N) acquisition in lichens, and to see whether different lichens differ in their affinity to various N sources, N uptake was measured in 14 various lichen associations ("species"). These species represented various morphologies (fruticose or foliose), contrasting microhabitat preferences (epiphytic or terricolous), and had green algal, cyanobacterial or both forms of photobionts. N was supplied under non-limiting conditions as an amino acid mixture, ammonium, or nitrate, using 15N to quantify uptake. Carbonyl cyanide m-chlorophenylhydrazone (CCCP) was used to separate active and passive uptake. Thallus N, amino acids, soluble polyol concentrations, and the biont-specific markers chlorophyll a and ergosterol were quantified, aiming to test if these metabolites or markers were correlated with N uptake capacity. Ammonium uptake was significantly greater and to a higher extent passive, relative to the other two N sources. Nitrate uptake differed among lichen photobiont groups, cyanobacterial lichens having a lower uptake rate. All lichens had the capacity to assimilate amino acids, in many species at rates equal to nitrate uptake or even higher, suggesting that organic N compounds could potentially have an important role in the N nutrition of these organisms. There were no clear correlations between N uptake rates and any of the measured metabolites or markers. The relative uptake rates of ammonium, nitrate and amino acids were not related to morphology or microhabitat. PMID:15060826

  11. Is the effect of silicon on rice uptake of arsenate (AsV) related to internal silicon concentrations, iron plaque and phosphate nutrition?

    PubMed

    Guo, W; Zhu, Y-G; Liu, W-J; Liang, Y-C; Geng, C-N; Wang, S-G

    2007-07-01

    Solution culture experiments were conducted to investigate the effects of silicon (Si) on arsenate (As(V)) uptake by rice. The addition of Si to the pretreatment or uptake solution significantly decreased shoot and root As concentrations (P<0.001 and P<0.05). The presence of Si in the pretreatment or uptake solution also significantly decreased shoot P concentrations (P<0.001). The data demonstrated that both internal and external Si inhibited the uptake of As and P. Results of As uptake kinetics showed that the mechanism of the effect of Si on arsenate uptake is not caused by direct competition for active sites of transporters with As. The effect of Si on As uptake was not entirely mediated through the effect of Si on P uptake. Although the addition of Si to pretreatment solutions still significantly decreased shoot and root As concentrations, the extent of reduction became smaller when rice roots were coated with iron plaque. PMID:17175078

  12. In-111-labeled white blood cell uptake in noninfected closed fracture in humans: prospective study

    SciTech Connect

    Van Nostrand, D.; Abreu, S.H.; Callaghan, J.J.; Atkins, F.B.; Stoops, H.C.; Savory, C.G.

    1988-05-01

    Since indium-111 white blood cell (In-111 WBC) scintigraphy is often used to evaluate for osteomyelitis in bone fractures, it is important to know if noninfected fractures have In-111 WBC uptake. Twenty-seven noninfected closed fracture sites in 19 patients were prospectively evaluated with technetium-99m methylene diphosphonate bone scintigraphy and In-111 WBC scintigraphy. In-111 WBC uptake was present in 41% of the 27 sites. In the 11 positive sites, the In-111 WBC uptake was 1+ (definite but minimal) in 55%, 2+ (moderate) in 36%, and 3+ (marked) in 9%. The visual intensity of the radioactive uptake on In-111 WBC scintigrams relative to that on bone scintigrams was less in 82%, equal in 9%, and greater in 9%. The visual size of the area of uptake on In-111 WBC scintigrams and bone scintigrams was smaller in 36%, equal in 55%, and greater in 9%. Factors that may help distinction of In-111 WBC uptake due to fracture alone from infection associated with fracture are discussed.

  13. Ocean uptake of carbon dioxide

    SciTech Connect

    Peng, Tsung-Hung ); Takahashi, Taro . Lamont-Doherty Earth Observatory)

    1993-01-01

    Factors controlling the capacity of the ocean for taking up anthropogenic C0[sup 2] include carbon chemistry, distribution of alkalinity, pCO[sup 2] and total concentration of dissolved C0[sup 2], sea-air pCO[sup 2] difference, gas exchange rate across the sea-air interface, biological carbon pump, ocean water circulation and mixing, and dissolution of carbonate in deep sea sediments. A general review of these processes is given and models of ocean-atmosphere system based on our understanding of these regulating processes axe used to estimate the magnitude of C0[sup 2] uptake by the ocean. We conclude that the ocean can absorb up to 35% of the fossil fuel emission. Direct measurements show that 55% Of C0[sup 2] from fossil fuel burning remains in the atmosphere. The remaining 10% is not accounted for by atmospheric increases and ocean uptake. In addition, it is estimated that an amount equivalent to 30% of recent annual fossil fuel emissions is released into the atmosphere as a result of deforestation and farming. To balance global carbon budget, a sizable carbon sink besides the ocean is needed. Storage of carbon in terrestrial biosphere as a result of C0[sup 2] fertilization is a potential candidate for such missing carbon sinks.

  14. Ocean uptake of carbon dioxide

    SciTech Connect

    Peng, Tsung-Hung; Takahashi, Taro

    1993-06-01

    Factors controlling the capacity of the ocean for taking up anthropogenic C0{sup 2} include carbon chemistry, distribution of alkalinity, pCO{sup 2} and total concentration of dissolved C0{sup 2}, sea-air pCO{sup 2} difference, gas exchange rate across the sea-air interface, biological carbon pump, ocean water circulation and mixing, and dissolution of carbonate in deep sea sediments. A general review of these processes is given and models of ocean-atmosphere system based on our understanding of these regulating processes axe used to estimate the magnitude of C0{sup 2} uptake by the ocean. We conclude that the ocean can absorb up to 35% of the fossil fuel emission. Direct measurements show that 55% Of C0{sup 2} from fossil fuel burning remains in the atmosphere. The remaining 10% is not accounted for by atmospheric increases and ocean uptake. In addition, it is estimated that an amount equivalent to 30% of recent annual fossil fuel emissions is released into the atmosphere as a result of deforestation and farming. To balance global carbon budget, a sizable carbon sink besides the ocean is needed. Storage of carbon in terrestrial biosphere as a result of C0{sup 2} fertilization is a potential candidate for such missing carbon sinks.

  15. Cadmium uptake by floating macrophytes.

    PubMed

    Maine, M A; Duarte, M V; Suñé, N L

    2001-08-01

    Cd uptake capacity of a group of floating macrophytes (Salvinia herzogii, Pistia stratiotes, Hydromistia stolonifera and Eichhornia crassipes) was determined in outdoors experiments during the lowest temperature period of the year. Although all studied species were highly efficient in the Cd uptake, Pistia stratiotes was selected for further research because of its superior performance and its higher average relative growth rate. Cadmium% removal by Pistia stratiotes was greater in the first 24 h of the experiments (63, 65, 72 and 74% of the added Cd for 1, 2, 4 and 6 mg Cd 1(-1), respectively). After 31 days of growth, Pistia statiotes efficiently removed Cd at the studied concentrations. The macrophyte was able to keep its capacity for Cd removal even though some toxicity symptoms appeared at 4 and 6 mg Cd 1(-1). The greater the initial concentration, the greater Cd bioaccumulation rates. The increase of Cd concentration in plant tissues occurred especially in roots and was linearly related to the quantity of Cd added. Cd sorption by roots is faster than translocation to the plant aerial part and it occurs mainly during the first 24h. PMID:11456161

  16. Uptake of technetium-99m methylene diphosphonate by fractured and osteoporotic bone after a pulse dose of Vitamin D/sub 3/. [Rats

    SciTech Connect

    Carr, E.A. Jr.; Carroll, M.; Montes, M.; Zielezny, M.

    1985-04-01

    The effect of a pulse dose of Vitamin D/sub 3/ on uptake of (/sup 99m/Tc)MDP by fractured and osteoporotic bone, respectively, was compared with D/sub 3/'s effect on uptake by normal bone in rats. At 4, 7, and 14 days, respectively, after femoral fracture, basal uptake was significantly increased at the fracture site by 336.8, 276.1, and 183.5%, respectively, over the contralateral control site. D/sub 3/-treated rats had lower uptakes than untreated controls at all three fracture sites and at 12 of 15 normal bone sites but analysis of variance showed the uptake differences were not significant. Cortisone-induced osteoporosis caused a significant decrease in basal uptake. The decrease occurred in all nine bone areas studied. D/sub 3/ caused a significant increase in uptake by these osteoporotic bones, but a significant decrease in uptake by the same bones in normal controls. Thus, D/sub 3/ had an effect on uptake by the bone lesion, osteoporosis, that differed from D/sub 3/'s effect on uptake by fracture or normal bone.

  17. Cell uptake survey of pegylated nanographene oxide

    NASA Astrophysics Data System (ADS)

    Vila, M.; Portolés, M. T.; Marques, P. A. A. P.; Feito, M. J.; Matesanz, M. C.; Ramírez-Santillán, C.; Gonçalves, G.; Cruz, S. M. A.; Nieto, A.; Vallet-Regi, M.

    2012-11-01

    Graphene and more specifically, nanographene oxide (GO) has been proposed as a highly efficient antitumoral therapy agent. Nevertheless, its cell uptake kinetics, its influence in different types of cells and the possibility of controlling cellular internalization timing, is still a field that remains unexplored. Herein, different cell types have been cultured in vitro for several incubation periods in the presence of 0.075 mg ml-1 pegylated GO solutions. GO uptake kinetics revealed differences in the agent’s uptake amount and speed as a function of the type of cell involved. Osteoblast-like cells GO uptake is higher and faster without resulting in greater cell membrane damage. Moreover, the dependence on the commonly used PEG nature (number of branches) also influences the viability and cell uptake speed. These facts play an important role in the future definition of timing parameters and selective cell uptake control in order to achieve an effective therapy.

  18. Ethanol intake and sup 3 H-serotonin uptake II: A study in alcoholic patients using platelets sup 3 H-paroxetine binding

    SciTech Connect

    Daoust, M.; Boucly, P. ); Ernouf, D. ); Breton, P. ); Lhuintre, J.P.

    1991-01-01

    The kinetic parameters of {sup 3}H-paroxetine binding and {sup 3}H-serotonin uptake were studied in platelets of alcoholic patients. There was no difference between alcoholic and non alcoholic subjects in {sup 3}H-paroxetine binding. When binding and {sup 3}H-serotonin uptake were studied, in the same plasma of the same subjects, the Vmax of serotonin uptake was increased in alcoholics. The data confirm the involvement of serotonin uptake system in alcohol dependance and suggest that serotonin uptake and paroxetine binding sites may be regulated independently in this pathology.

  19. Calcium uptake in the skin of a freshwater teleost.

    PubMed

    McCormick, S D; Hasegawa, S; Hirano, T

    1992-04-15

    The skin, particularly the opercular membrane of some teleosts, contains mitochondrion-rich "chloride" cells and has been widely used as a model to study branchial salt-extrusion mechanisms in seawater fish. Skin isolated from the operculum of the freshwater Nile tilapia (Oreochromis niloticus) can transport Ca2+ against an ionic and electrical gradient. Adaptation of Nile tilapia to a low-Ca2+ environment increased the capacity of the opercular membrane to transport Ca2+. The density of mitochondrion-rich cells increased in parallel with Ca2+ transport capacity. The results demonstrate net Ca2+ uptake by vertebrate skin and strongly implicate mitochondrion-rich cells as the site of Ca2+ uptake in fresh water. PMID:1565659

  20. Monitoring iron uptake by siderophores.

    PubMed

    Hoegy, Françoise; Schalk, Isabelle J

    2014-01-01

    Iron is an important element for almost all forms of life. In order to get access to this essential nutriment, Pseudomonads produce two major siderophores, pyoverdine PVD and pyochelin (PCH). Uptake of iron in bacterial cells can be monitored accurately using (55)Fe. Bacteria cells are incubated in the presence of either PVD or PCH loaded with (55)Fe. After incubation, extracellular iron ions are separated from those accumulated in the bacteria cells by either centrifugation or filtration on glass microfiber filters, for the PCH and PVD assays, respectively. (55)Fe contained in the harvested cells on the filter or in the cell pellet is counted in scintillation cocktail. The number of moles of (55)Fe transported can be determined using the specific activity of the radionuclide. PMID:24818918

  1. Uptake, Distribution and Speciation of Chromium

    SciTech Connect

    Bluskov,S.; Arocena, J.; Omotoso, O.; Young, J.

    2005-01-01

    Brassica juncea (Indian mustard) has been widely used in phytoremediation because of its capacity to accumulate high levels of chromium (Cr) and other metals. The present study was conducted to investigate mechanism(s) involved in Cr binding and sequestration by B. juncea. The plants were grown under greenhouse conditions in field-moist or air-dried soils, amended with 100 mg kg -1 of Cr (III or VI). The plant concentrated Cr mainly in the roots. B. juncea removed an average of 48 and 58 {mu}g Cr per plant from Cr (III) and Cr (VI)-treated soils, respectively. The uptake of Cr was not affected by the moisture status of the soils. X-ray absorption near-edge spectroscopy measurements showed only Cr (III) bound predominantly to formate and acetate ligands, in the bulk and rhizosphere soils, respectively. In the plant tissues, Cr (III) was detected, primarily as acetate in the roots and oxalate in the leaves. X-ray microprobe showed the sites of Cr localization, and probably sequestration, in epidermal and cortical cells in the roots and epidermal and spongy mesophyll cells in the leaves. These findings demonstrate the ability of B. juncea to detoxify more toxic Cr (VI), thereby making this plant a potential candidate for phytostabilization.

  2. Lysimeter study of vegetative uptake from saltstone

    SciTech Connect

    Murphy, C.E. Jr.

    1990-06-08

    At the Savannah River Site, liquid, low-level nuclear waste will be disposed of by incorporating the waste in concrete, a wasteform called saltstone. Saltstone monoliths will then be buried in the earth. To study the potential uptake of radionuclides by trees and other plants growing in the soil in the area containing buried saltstone, a lysimeter study has been in progress since 1984. Thirty two lysimeters were designed, constructed, and filled with soil. Saltstone samples, containing the liquid, low-level supernate from the tank 50 in-tank precipitation demonstration, were buried in some of the lysimeters. Other lysimeters, not containing saltstone, were used as controls. Crops, grass, and trees were planted in the lysimeters and sampled periodically to determine radionuclide concentrations. Water samples were also collected from the lysimeter sumps and analyzed for radionuclide content. This report documents the results of vegetative and lysimeter sump water measurements from the beginning of the project in November of 1984 through September of 1989. 6 refs., 22 figs., 6 tabs.

  3. Effect of Uptake-one inhibitors on the uptake of norepinephrine and metaiodobenzylguanidine

    SciTech Connect

    Tobes, M.C.; Jaques, S. Jr.; Wieland, D.M.; Sisson, J.C.

    1985-08-01

    The mechanisms underlying the uptake of the radiopharmaceutical metaiodobenzylguanidine (MIBG) and the catecholamine norepinephrine (NE) were studied using cultured bovine adrenomedullary cells as an in vitro model system. Sodium-dependent and sodium-independent uptake systems have been identified and characterized for both MIBG and NE. The sodium-dependent uptake of Ne and MIBG was inhibited by the selective Uptake-one inhibitors, desmethylimipramine (DMI) and cocaine, whereas the sodium-independent uptake for NE and MIBG was much less sensitive to inhibition by these agents. The sodium-dependent uptake system fulfills the criteria for the neuronal Uptake-one system, and the sodium-independent uptake system fulfills the criteria for a passive diffusion mechanism. Arterial concentrations proximal to the dog adrenal were very small suggesting that the sodium-dependent (Uptake-one) system is predominant in vivo. Consistent with the in vitro observations, the in vivo uptake of MIBG and NE into dog adrenal medullae was effectively blocked by pretreatment with DMI or cocaine. Therefore, iodine-131 MIBG scintigraphy of the adrenal appears to reflect uptake by way of the Uptake-one system.

  4. Comparative uptake kinetics and transport of cadmium and phosphate in Phleum pratense-Glomus deserticolum associations

    SciTech Connect

    Arnold, P.T.; Kapustka, L.A. )

    1993-01-01

    Mycorrhizal plants (timothy grass, Phleum pretense with Glomus deserticolum) were compared to nonmycorrhizal timothy grass to determine the effect of the mycorrhizal condition on the uptake and transport of cadmium. Companion experiments were conducted to ascertain phosphate uptake kinetics of mycorrhizal and nonmycorrhizal plants. Divalent cation competition experiments also were employed in this study. Comparisons of the high-affinity uptake mechanisms between mycorrhizal and nonmycorrhizal plants identified higher levels of phosphate uptake were due to an increase in the number of uptake sites rather than to differences in affinity. The respective values for K[sub m] for high-affinity phosphate uptake were 2.5 [plus minus] 1.3 [mu]MP (mycorrhizal) and 3.4 [plus minus] 1.3 [mu]MP (nonmycorrhizal), but these values were not statistically different at the [alpha] = 0.05 level. High-affinity Cd[sup 2+] uptake differed significantly between mycorrhizal (4.5 [plus minus] 2.8 [mu]M) and nonmycorrhizal (2.8 [plus minus] 1.1 [mu]M) plants. Presence of Ca[sup 2+] at 1.0mM concentration conferred considerable competitive protection in both the mycorrhizal and the nonmycorrhizal conditions. The effect of Ca[sup 2+] was an approximate fourfold increase in the respective K[sub m] values.

  5. Glucose metabolism in sediments of a eutrophic lake: tracer analysis of uptake and product formation.

    PubMed

    King, G M; Klug, M J

    1982-12-01

    The uptake of glucose and the formation of end products from glucose catabolism have been measured for sediments of eutrophic Wintergreen Lake with a combination of tritiated and C-labeled tracers. Time course analyses of the loss of [H]glucose from sediments were used to establish rate constants for glucose uptake at natural substrate concentrations. Turnover times from these analyses were about 1 min for littoral and profundal sediments. No seasonal or site differences were noted in turnover times. Time course analyses of [U-C]glucose uptake and C-labeled end product formation indicated that glucose mass flow could not be calculated from end product formation since the specific activity of added [C]glucose was significantly diluted by pools of intracellular glucose and glucose metabolites. Mass flow could only be accurately estimated by use of rates of uptake from tracer studies. Intermediate fermentation end products included acetate (71%), propionate (15%), lactate (9%), and only minor amounts of butyrates or valerates. Addition of H(2) to sediments resulted in greater production of lactate (28%) and decreased formation of acetate (50%), but did not affect glucose turnover. Depth profiles of glucose uptake indicated that rates of uptake decreased with depth over the 0- to 18-cm interval and that glucose uptake accounted for 30 to 40% of methanogenesis in profundal sediments. PMID:16346148

  6. Kinetic studies of the uptake of aspartate aminotransferase and malate dehydrogenase into mitochondria in vitro.

    PubMed Central

    Marra, E; Passarella, S; Casamassima, E; Perlino, E; Doonan, S; Quagliariello, E

    1985-01-01

    Kinetic measurements of the uptake of native mitochondrial aspartate aminotransferase and malate dehydrogenase into mitochondria in vitro were carried out. The uptake of both the enzymes is essentially complete in 1 min and shows saturation characteristics. The rate of uptake of aspartate aminotransferase into mitochondria is decreased by malate dehydrogenase, and vice versa. The inhibition is exerted by isoenzyme remaining outside the mitochondria rather than by isoenzyme that has been imported. The thiol compound beta-mercaptoethanol decreases the rate of uptake of the tested enzymes; inhibition is a result of interaction of beta-mercaptoethanol with the mitochondria and not with the enzymes themselves. The rate of uptake of aspartate aminotransferase is inhibited non-competitively by malate dehydrogenase, but competitively by beta-mercaptoethanol. The rate of uptake of malate dehydrogenase is inhibited non-competitively by aspartate aminotransferase and by beta-mercaptoethanol. beta-Mercaptoethanol prevents the inhibition of the rate of uptake of malate dehydrogenase by aspartate aminotransferase. These results are interpreted in terms of a model system in which the two isoenzymes have separate but interacting binding sites within a receptor in the mitochondrial membrane system. PMID:4015628

  7. Nitrite Uptake into Intact Pea Chloroplasts 1

    PubMed Central

    Brunswick, Pamela; Cresswell, Christopher F.

    1988-01-01

    The relationship between net nitrite uptake and its reduction in intact pea chloroplasts was investigated employing electron transport regulators, uncouplers, and photophosphorylation inhibitors. Observations confirmed the dependence of nitrite uptake on stromal pH and nitrite reduction but also suggested a partial dependance upon PSI phosphorylation. It was also suggested that ammonia stimulates nitrogen assimilation in the dark by association with stromal protons. Inhibition of nitrite uptake by N-ethylmaleimide and dinitrofluorobenzene could not be completely attributed to their inhibition of carbon dioxide fixation. Other protein binding reagents which inhibited photosynthesis showed no effect on nitrite uptake, except for p-chlormercuribenzoate which stimulated nitrite uptake. The results with N-ethylmaleimide and dinitrofluorobenzene tended to support the proposed presence of a protein permeation channel for nitrite uptake in addition to HNO2 penetration. On the basis of a lack of effect by known anion uptake inhibitors, it was concluded that the nitrite uptake mechanism was distinct from that of phosphate and chloride/sulfate transport. PMID:16665917

  8. Learner Uptake in Communicative ESL Lessons.

    ERIC Educational Resources Information Center

    Ellis, Rod; Basturkmen, Helen; Loewen, Shawn

    2001-01-01

    Examines incidental and transitory focus on form. Learner uptake was studied in focus-on-form episodes occurring in 12 hours of communicative English-as-a-Second-Language teaching. Learner uptake was generally high and successful--to a much greater extent than has been reported for immersion classrooms. (Author/VWL)

  9. Gallium-67 pulmonary uptake in eosinophilic pneumonia

    SciTech Connect

    Morais, J.; Carrier, L.; Gariepy, G.; Le Bel, L.; Chartrand, R.; Picard, D.

    1988-01-01

    Eosinophilic pneumonia is usually diagnosed based on the findings on chest x-ray, white blood count, and transbronchial biopsy. After reporting a case of Ga-67 lung uptake in eosinophilic pneumonia, its histopathology is discussed and the mechanisms of Ga-67 uptake by inflammatory lesions are reviewed.

  10. Decreased gallium uptake in acute hematogenous osteomyelitis

    SciTech Connect

    Ang, J.G.; Gelfand, M.J.

    1983-07-01

    Decreased radiopharmaceutical uptake was noted on both bone and gallium scans in the case of acute hematogenous osteomyelitis of the right ilium (acetabular roof). This combination of findings is probably rare. The mechanism of decreased gallium uptake is unknown, but may be related to decreased blood flow.

  11. Groundwater ecohydrology: phreatophyte root uptake of groundwater

    NASA Astrophysics Data System (ADS)

    Steward, D. R.

    2008-12-01

    An analytic solution is presented for groundwater uptake by phreatophytes. This solution is developed for individual phreatophytes with prescribed mathematical forms of groundwater uptake beneath the plant. As this function is linear, mathematical solutions may be superimposed to simulate groundwater uptake by a field of phreatophytes. A simpler representation of groundwater uptake by a field of phreatophytes is developed through aid of the Analytic Element Method. This, too, may be superimposed as the functions are linear to simulate groundwater flow associated with fields of phreatophytes. Together, this provides a computationally effective means to simulate the detailed local groundwater flow field associated with uptake by a phreatophyte within a regional groundwater flow field. Results illustrate the spatial patterns that emerge from localized groundwater extractions within fields of phreatophytes.

  12. Cadmium and calcium uptake in the mollusc donax rugosus and effect of a calcium channel blocker

    SciTech Connect

    Sidoumou, Z.; Gnassia-Barelli, M.; Romeo, M.

    1997-02-01

    Donax rugosus, a common bivalve mollusc in the coastal waters of Mauritania, has been studied for trace metal concentrations as a function of sampling site (from South of Mauritania to the North of this country) and of season. In this paper, the uptake of cadmium was experimentally studied in the different organs of D. rugosus. Since metals such as cadmium, copper and mercury may alter calcium homeostasis, calcium uptake was also studied in the animals treated with cadmium. Since calcium is taken up through specific channels, it appears that metals inhibit Ca uptake by interacting with these channels in the plasma membrane. Cadmium and calcium have very similar atomic radii, thus cadmium may be taken up through the calcium channels, particularly through voltage-dependent channels. The uptake of cadmium and calcium by D. Rugosus was therefore also studied in the presence of the calcium channel blocker verapamil. 13 refs., 3 figs., 1 tab.

  13. Phytoplankton productivity, respiration, and nutrient uptake and regeneration in the Potomac River, August 1977 - August 1978

    USGS Publications Warehouse

    Cole, B.E.; Harmon, D.D.

    1981-01-01

    Rates of phytoplankton productivity, respiration, and nutrient uptake and regeneration are presented. These observations were made on the Potomac River estuary (POTE) during four cruises between August 1977 and August 1978. Four experimental methods were used: carbon uptake using carbon-14, carbon uptake and respiration by a pH method, productivity and respiration by the dissolved oxygen method, and nutrient (NH4+, NO3-, NO2-, PO4=, and SiO2=) uptake and regeneration by colorimetry. The experiments were made at sites representative of conditions in four principal reaches of the tidal Potomac River estuary: near the mouth, seaward of the summer nutrient and phytoplankton maximum, near the region of maximum phytoplankton standing stock , and near the maximum anthropogenic nutrient source. (USGS)

  14. Controls on tree water uptake and information storage in tree rings

    NASA Astrophysics Data System (ADS)

    Blume, Theresa; Simard, Sonia; Heidbüchel, Ingo; Güntner, Andreas; Heinrich, Ingo

    2016-04-01

    Controls on tree water uptake are investigated in various forest stands in the northeastern German lowlands by a multi-method approach. This approach combines sapflow and dendrometer measurements as well as tree-ring analyses with soil moisture derived root water uptake rates. The latter method has the advantage that it provides depth distributions of root water uptake and thus additional information allowing for a more detailed analysis of the relationship between water availability and water uptake. High resolution climatic data makes it possible to investigate the site specific interplay between atmospheric demand and water availability on the one hand and tree response and adaptation on the other hand. The comparison of spatio-temporal patterns of these responses with concurrent tree growth as well as tree-ring analyses enables a first matching of actual and "archived" patterns and thus an estimate of how much of this information is stored in tree rings.

  15. Time course of ouabain uptake in isolated myocardial cells: dependence on extracellular potassium and calcium concentration.

    PubMed Central

    Meldgaard, L.; Steiness, E.; Waldorff, S.

    1981-01-01

    1 Spontaneously beating myocardial cells isolated from newborn rats have been used to evaluate the time course of cellular ouabain uptake. 2 The rate of cellular uptake and the amount of ouabain bound at equilibrium were computed by fitting the experimental data to the conventional exponential equation for receptor binding of drugs. 3 At normal extracellular potassium and calcium concentrations a biexponential equation was the best fit to the experimental data, indicating two receptor sites of ouabain with different rates of uptake. 4 Increasing extracellular potassium or calcium concentrations decreased the amounts of ouabain bound at equilibrium. 5 High and low extracellular concentrations of potassium or calcium decreased the rate of ouabain uptake. 6 It is well known that ouabain changes ionic fluxes. Changes in the extracellular potassium and calcium concentrations also influence the amount of ouabain taken up by myocardial cells, as demonstrated in the present study. PMID:7236989

  16. Uptake of indium-111-labeled leukocytes by brain metastasis

    SciTech Connect

    Balachandran, S.; Husain, M.M.; Adametz, J.R.; Pallin, J.S.; Angtuaco, T.L.; Boyd, C.M.

    1987-04-01

    Uptake of indium-labeled leukocytes was seen in two cases of histologically proven brain metastasis. In one, this led to misdiagnosis of the lesion as an abscess. On histological evaluation, a large number of white blood cells or macrophages was seen at the neoplastic sites. Reasons for leukocyte accumulation around metastatic brain neoplasms are discussed. In contrast to the current reports that indium-labeled leukocyte scans can differentiate intracranial infection from tumor, these cases demonstrate their lack of specificity in the detection of brain abscess.

  17. Temperature responses of carbon monoxide and hydrogen uptake by vegetated and unvegetated volcanic cinders

    PubMed Central

    King, Caitlin E; King, Gary M

    2012-01-01

    Ecosystem succession on a large deposit of volcanic cinders emplaced on Kilauea Volcano in 1959 has resulted in a mosaic of closed-canopy forested patches and contiguous unvegetated patches. Unvegetated and unshaded surface cinders (Bare) experience substantial diurnal temperature oscillations ranging from moderate (16 °C) to extreme (55 °C) conditions. The surface material of adjacent vegetated patches (Canopy) experiences much smaller fluctuations (14–25 °C) due to shading. To determine whether surface material from these sites showed adaptations by carbon monoxide (CO) and hydrogen (H2) consumption to changes in ambient temperature regimes accompanying succession, we measured responses of CO and H2 uptake to short-term variations in temperature and long-term incubations at elevated temperature. Based on its broader temperature optimum and lower activation energy, Canopy H2 uptake was less sensitive than Bare H2 uptake to temperature changes. In contrast, Bare and Canopy CO uptake responded similarly to temperature during short-term incubations, indicating no differences in temperature sensitivity. However, during extended incubations at 55 °C, CO uptake increased for Canopy but not Bare material, which indicated that the former was capable of thermal adaptation. H2 uptake for material from both sites was completely inhibited at 55 °C throughout extended incubations. These results indicated that plant development during succession did not elicit differences in short-term temperature responses for Bare and Canopy CO uptake, in spite of previously reported differences in CO oxidizer community composition, and differences in average daily and extreme temperatures. Differences associated with vegetation due to succession did, however, lead to a notable capacity for thermophilic CO uptake by Canopy but not Bare material. PMID:22258097

  18. Plant-uptake of uranium: Hydroponic and soil system studies

    USGS Publications Warehouse

    Ramaswami, A.; Carr, P.; Burkhardt, M.

    2001-01-01

    Limited information is available on screening and selection of terrestrial plants for uptake and translocation of uranium from soil. This article evaluates the removal of uranium from water and soil by selected plants, comparing plant performance in hydroponic systems with that in two soil systems (a sandy-loam soil and an organic-rich soil). Plants selected for this study were Sunflower (Helianthus giganteus), Spring Vetch (Vicia sativa), Hairy Vetch (Vicia villosa), Juniper (Juniperus monosperma), Indian Mustard (Brassica juncea), and Bush Bean (Phaseolus nanus). Plant performance was evaluated both in terms of the percent uranium extracted from the three systems, as well as the biological absorption coefficient (BAC) that normalized uranium uptake to plant biomass. Study results indicate that uranium extraction efficiency decreased sharply across hydroponic, sandy and organic soil systems, indicating that soil organic matter sequestered uranium, rendering it largely unavailable for plant uptake. These results indicate that site-specific soils must be used to screen plants for uranium extraction capability; plant behavior in hydroponic systems does not correlate well with that in soil systems. One plant species, Juniper, exhibited consistent uranium extraction efficiencies and BACs in both sandy and organic soils, suggesting unique uranium extraction capabilities.

  19. Cystine and dibasic amino acid uptake by opossum kidney cells

    SciTech Connect

    States, B.; Segal, S. )

    1990-06-01

    The characteristics of the uptake of L-cystine by the continuous opossum kidney cell line, OK, were examined. Uptake of cystine is rapid and, in contrast to other continuous cultured cell lines, these cells retain the cystine/dibasic amino acid transport system which is found in vivo and in freshly isolated kidney tissue. Confluent monolayers of cells also fail to show the presence of the cystine/glutamate transport system present in LLC-PK1 cells, fibroblasts, and cultured hepatocytes. Uptake of cystine occurs via a high-affinity saturable process which is independent of medium sodium concentration. The predominant site of cystine transport is across the apical cell membrane. The intracellular concentration of GSH far exceeds that of cystine with a ratio greater than 100:1 for GSH:cysteine. Incubation of cells for 5 minutes with a physiological level of labelled cystine resulted in the labelling of 66% and 5% of the total intracellular cysteine and glutathione, respectively. The ability of these cells to reflect the shared cystine/dibasic amino acid transport system makes them a suitable model for investigation of the cystine carrier which is altered in human cystinuria.

  20. A statistical approach to estimate O3 uptake of ponderosa pine in a mediterranean climate.

    PubMed

    Grulke, N E; Preisler, H K; Fan, C C; Retzlaff, W A

    2002-01-01

    In highly polluted sites, stomatal behavior is sluggish with respect to light, vapor pressure deficit, and internal CO2 concentration (Ci) and poorly described by existing models. Statistical models were developed to estimate stomatal conductance (gs) of 40-year-old ponderosa pine at three sites differing in pollutant exposure for the purpose of calculating O3 uptake. Gs was estimated using julian day, hour of day, pre-dawn xylem potential and photosynthetic photon flux density (PPFD). The median difference between estimated and observed field gs did not exceed 10 mmol H2O m(-2) s(-1), and estimated gs within 95% confidence intervals. 03 uptake was calculated from hourly estimated gs, hourly O3 concentration, and a constant to correct for the difference in diffusivity between water vapor and 03. The simulation model TREGRO was also used to calculate the cumulative 03 uptake at all three sites. 03 uptake estimated by the statistical model was higher than that simulated by TREGRO because gas exchange rates were proportionally higher. O3 exposure and uptake were significantly correlated (r2>0.92), because O3 exposure and gs were highly correlated in both statistical and simulation models. PMID:12152824

  1. Mercury uptake into poplar leaves.

    PubMed

    Assad, Mohamad; Parelle, Julien; Cazaux, David; Gimbert, Frédéric; Chalot, Michel; Tatin-Froux, Fabienne

    2016-03-01

    Tailings dumps require mercury stabilization to prevent air pollution by evaporated mercury, which can be achieved through plant covers. Plants are considered a net sink for atmospheric Hg via incorporation into leaf tissues. However, most studies related to Hg uptake by plants have considered plants exposed to only atmospheric Hg, whereas in the case of tailings dumps, plants are potentially exposed to both soil and atmospheric Hg. The goal of this work is to evaluate the relative contributions of root and atmospheric pathways by growing poplar (Populus trichocarpa X Populus maximowiczii/var Skado) cuttings on either control or polluted substrates and under either natural or controlled exposure conditions. We showed that foliar Hg concentrations significantly increased with age, reaching 120 ng g(-1) dry mass when poplars were exposed to Hg-contaminated substrate under natural exposure. Remarkably, we did not observe significantly different Hg concentrations in poplar leaves grown on either the control or polluted substrates when cultivated together in growth chambers. Our set of data prompted us to conclude that Hg entry into poplar leaves is exclusively through an atmospheric pathway. Our results are discussed in line with existing literature. PMID:26694893

  2. Saturable Hepatic Extraction of Gemcitabine Involves Biphasic Uptake Mediated by Nucleoside Transporters Equilibrative Nucleoside Transporter 1 and 2.

    PubMed

    Shimada, Takuya; Nakanishi, Takeo; Tajima, Hidehiro; Yamazaki, Maiko; Yokono, Rina; Takabayashi, Makiko; Shimada, Tsutomu; Sawamoto, Kazuki; Miyamoto, Ken-Ichi; Kitagawa, Hirohisa; Ohta, Tetsuo; Tamai, Ikumi; Sai, Yoshimichi

    2015-09-01

    Hepatic arterial infusion (HAI) chemotherapy with gemcitabine (GEM) is expected to be more effective and safer method to treat hepatic metastasis of pancreatic cancer compared with intravenous administration, because it affords higher tumor exposure with lower systemic exposure. Thus, a key issue for dose selection is the saturability of hepatic uptake of GEM. Therefore, we investigated GEM uptake in rat and human isolated hepatocytes. Hepatic GEM uptake involved high- and low-affinity saturable components with Km values of micromolar and millimolar order, respectively. The uptake was inhibited concentration dependently by S-(4-nitrobenzyl)-6-thioinosine (NBMPR) and was sodium-ion-independent, suggesting a contribution of equilibrative nucleoside transporters (ENTs). The concentration dependence of uptake in the presence of 0.1 μM NBMPR showed a single low-affinity binding site. Therefore, the high- and low-affinity sites correspond to ENT1 and ENT2, respectively. Our results indicate hepatic extraction of GEM is predominantly mediated by the low-affinity site (hENT2), and at clinically relevant hepatic concentrations of GEM, hENT2-mediated uptake would not be completely saturated. This is critical for HAI, because saturation of hepatic uptake would result in a marked increase of GEM concentration in the peripheral circulation, abrogating the advantage of HAI over intravenous administration in terms of severe adverse events. PMID:26037416

  3. A bioluminescent assay for measuring glucose uptake.

    PubMed

    Valley, Michael P; Karassina, Natasha; Aoyama, Natsuyo; Carlson, Coby; Cali, James J; Vidugiriene, Jolanta

    2016-07-15

    Identifying activators and inhibitors of glucose uptake is critical for both diabetes management and anticancer therapy. To facilitate such studies, easy-to-use nonradioactive assays are desired. Here we describe a bioluminescent glucose uptake assay for measuring glucose transport in cells. The assay is based on the uptake of 2-deoxyglucose and the enzymatic detection of the 2-deoxyglucose-6-phosphate that accumulates. Uptake can be measured from a variety of cell types, it can be inhibited by known glucose transporter inhibitors, and the bioluminescent assay yields similar results when compared with the radioactive method. With HCT 116 cells, glucose uptake can be detected in as little as 5000 cells and remains linear up to 50,000 cells with signal-to-background values ranging from 5 to 45. The assay can be used to screen for glucose transporter inhibitors, or by multiplexing with viability readouts, changes in glucose uptake can be differentiated from overall effects on cell health. The assay also can provide a relevant end point for measuring insulin sensitivity. With adipocytes and myotubes, insulin-dependent increases in glucose uptake have been measured with 10- and 2-fold assay windows, respectively. Significant assay signals of 2-fold or more have also been measured with human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and skeletal myoblasts. PMID:27130501

  4. FDG uptake, a surrogate of tumour hypoxia?

    PubMed Central

    Van de Wiele, Christophe

    2008-01-01

    Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-d-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting. PMID:18509637

  5. Aminoglycoside uptake increased by tet gene expression.

    PubMed Central

    Merlin, T L; Davis, G E; Anderson, W L; Moyzis, R K; Griffith, J K

    1989-01-01

    The expression of extrachromosomal tet genes not only confers tetracycline resistance but also increases the susceptibilities of gram-negative bacteria to commonly used aminoglycoside antibiotics. We investigated the possibility that tet expression increases aminoglycoside susceptibility by increasing bacterial uptake of aminoglycoside. Studies of [3H]gentamicin uptake in paired sets of Escherichia coli HB101 and Salmonella typhimurium LT2 expressing and not expressing tet showed that tet expression accelerates energy-dependent [3H]gentamicin uptake. Increased [3H]gentamicin uptake was accompanied by decreased bacterial protein synthesis and bacterial growth. Increased aminoglycoside uptake occurred whether tet expression was constitutive or induced, whether the tet gene was class B or C, and whether the tet gene was plasmid borne or integrated into the bacterial chromosome. tet expression produced no measurable change in membrane potential, suggesting that tet expression increases aminoglycoside uptake either by increasing the availability of specific carriers or by lowering the minimum membrane potential that is necessary for uptake. PMID:2684011

  6. Does elevated CO2 alter silica uptake in trees?

    DOE PAGESBeta

    Fulweiler, Robinson W.; Maguire, Timothy J.; Carey, Joanna C.; Finzi, Adrien C.

    2015-01-13

    Human activities have greatly altered global carbon (C) and Nitrogen (N) cycling. In fact, atmospheric concentrations of carbon dioxide (CO2) have increased 40% over the last century and the amount of N cycling in the biosphere has more than doubled. In an effort to understand how plants will respond to continued global CO2 fertilization, longterm free-air CO2 enrichment experiments have been conducted at sites around the globe. Here we examine how atmospheric CO2 enrichment and N fertilization affects the uptake of silicon (Si) in the Duke Forest, North Carolina, a stand dominated by Pinus taeda (loblolly pine), and five hardwoodmore » species. Specifically, we measured foliar biogenic silica concentrations in five deciduous and one coniferous species across three treatments: CO2 enrichment, N enrichment, and N and CO2 enrichment. We found no consistent trends in foliar Si concentration under elevated CO2, N fertilization, or combined elevated CO2 and N fertilization. However, two-thirds of the tree species studied here have Si foliar concentrations greater than well-known Si accumulators, such as grasses. Based on net primary production values and aboveground Si concentrations in these trees, we calculated forest Si uptake rates under control and elevated CO2 concentrations. Due largely to increased primary production, elevated CO2 enhanced the magnitude of Si uptake between 20 and 26%, likely intensifying the terrestrial silica pump. This uptake of Si by forests has important implications for Si export from terrestrial systems, with the potential to impact C sequestration and higher trophic levels in downstream ecosystems.« less

  7. Does elevated CO2 alter silica uptake in trees?

    PubMed

    Fulweiler, Robinson W; Maguire, Timothy J; Carey, Joanna C; Finzi, Adrien C

    2014-01-01

    Human activities have greatly altered global carbon (C) and Nitrogen (N) cycling. In fact, atmospheric concentrations of carbon dioxide (CO2) have increased 40% over the last century and the amount of N cycling in the biosphere has more than doubled. In an effort to understand how plants will respond to continued global CO2 fertilization, long-term free-air CO2 enrichment experiments have been conducted at sites around the globe. Here we examine how atmospheric CO2 enrichment and N fertilization affects the uptake of silicon (Si) in the Duke Forest, North Carolina, a stand dominated by Pinus taeda (loblolly pine), and five hardwood species. Specifically, we measured foliar biogenic silica concentrations in five deciduous and one coniferous species across three treatments: CO2 enrichment, N enrichment, and N and CO2 enrichment. We found no consistent trends in foliar Si concentration under elevated CO2, N fertilization, or combined elevated CO2 and N fertilization. However, two-thirds of the tree species studied here have Si foliar concentrations greater than well-known Si accumulators, such as grasses. Based on net primary production values and aboveground Si concentrations in these trees, we calculated forest Si uptake rates under control and elevated CO2 concentrations. Due largely to increased primary production, elevated CO2 enhanced the magnitude of Si uptake between 20 and 26%, likely intensifying the terrestrial silica pump. This uptake of Si by forests has important implications for Si export from terrestrial systems, with the potential to impact C sequestration and higher trophic levels in downstream ecosystems. PMID:25628636

  8. Does elevated CO2 alter silica uptake in trees?

    PubMed Central

    Fulweiler, Robinson W.; Maguire, Timothy J.; Carey, Joanna C.; Finzi, Adrien C.

    2015-01-01

    Human activities have greatly altered global carbon (C) and Nitrogen (N) cycling. In fact, atmospheric concentrations of carbon dioxide (CO2) have increased 40% over the last century and the amount of N cycling in the biosphere has more than doubled. In an effort to understand how plants will respond to continued global CO2 fertilization, long-term free-air CO2 enrichment experiments have been conducted at sites around the globe. Here we examine how atmospheric CO2 enrichment and N fertilization affects the uptake of silicon (Si) in the Duke Forest, North Carolina, a stand dominated by Pinus taeda (loblolly pine), and five hardwood species. Specifically, we measured foliar biogenic silica concentrations in five deciduous and one coniferous species across three treatments: CO2 enrichment, N enrichment, and N and CO2 enrichment. We found no consistent trends in foliar Si concentration under elevated CO2, N fertilization, or combined elevated CO2 and N fertilization. However, two-thirds of the tree species studied here have Si foliar concentrations greater than well-known Si accumulators, such as grasses. Based on net primary production values and aboveground Si concentrations in these trees, we calculated forest Si uptake rates under control and elevated CO2 concentrations. Due largely to increased primary production, elevated CO2 enhanced the magnitude of Si uptake between 20 and 26%, likely intensifying the terrestrial silica pump. This uptake of Si by forests has important implications for Si export from terrestrial systems, with the potential to impact C sequestration and higher trophic levels in downstream ecosystems. PMID:25628636

  9. Development of Plate Reader and On-Line Microfluidic Screening to Identify Ligands of the 5-Hydroxytryptamine Binding Protein in Venoms.

    PubMed

    Otvos, Reka A; Iyer, Janaki Krishnamoorthy; van Elk, René; Ulens, Chris; Niessen, Wilfried M A; Somsen, Govert W; Kini, R Manjunatha; Smit, August B; Kool, Jeroen

    2015-07-01

    The 5-HT3 receptor is a ligand-gated ion channel, which is expressed in the nervous system. Its antagonists are used clinically for treatment of postoperative- and radiotherapy-induced emesis and irritable bowel syndrome. In order to better understand the structure and function of the 5-HT3 receptor, and to allow for compound screening at this receptor, recently a serotonin binding protein (5HTBP) was engineered with the Acetylcholine Binding Protein as template. In this study, a fluorescence enhancement assay for 5HTBP ligands was developed in plate-reader format and subsequently used in an on-line microfluidic format. Both assay types were validated using an existing radioligand binding assay. The on-line microfluidic assay was coupled to HPLC via a post-column split which allowed parallel coupling to a mass spectrometer to collect MS data. This high-resolution screening (HRS) system is well suitable for compound mixture analysis. As a proof of principle, the venoms of Dendroapsis polylepis, Pseudonaja affinis and Pseudonaja inframacula snakes were screened and the accurate masses of the found bioactives were established. To demonstrate the subsequent workflow towards structural identification of bioactive proteins and peptides, the partial amino acid sequence of one of the bioactives from the Pseudonaja affinis venom was determined using a bottom-up proteomics approach. PMID:26114334

  10. Application of the flow cytometry for determination of the amount of DNA in Yersinia pestis cells under the influence of serotonin (5-hydroxytryptamine)

    NASA Astrophysics Data System (ADS)

    Korsukov, Vladimir N.; Shchukovskaya, Tatyana N.; Kravtsov, Alexander L.; Popov, Youri A.

    2002-07-01

    Using flow cytometry a low DNA content in inoculated Yersinia pestis EV cells have been shown at the beginning of culture in Hottinger broth pH 7.2. The dependence serotonin action of its concentration on DNA content have been demonstrated. Serotonin accelerated Yersinia pestis culture growth during cultivation in Hottinger broth pH 7.2 both at 28 degrees C and 37 degrees C at concentration of 10-5 M.

  11. Stress-Induced Depression Is Alleviated by Aerobic Exercise Through Up-Regulation of 5-Hydroxytryptamine 1A Receptors in Rats

    PubMed Central

    Kim, Tae Woon; Lim, Baek Vin; Baek, Dongjin; Ryu, Dong-Soo; Seo, Jin Hee

    2015-01-01

    Purpose: Stress is associated with depression, which induces many psychiatric disorders. Serotonin, also known as 5-hydroxy-tryptamine (5-HT), acts as a biochemical messenger and regulator in the brain. It also mediates several important physiological functions. Depression is closely associated with an overactive bladder. In the present study, we investigated the effect of treadmill exercise on stress-induced depression while focusing on the expression of 5-HT 1A (5-H1A) receptors in the dorsal raphe. Methods: Stress was induced by applying a 0.2-mA electric foot shock to rats. Each set of electric foot shocks comprised a 6-second shock duration that was repeated 10 times with a 30-second interval. Three sets of electric foot shocks were applied each day for 7 days. For the confirmation of depressive state, a forced swimming test was performed. To visualize the expression of 5-HT and tryptophan hydroxylase (TPH), immunohistochemistry for 5-HT and TPH in the dorsal raphe was performed. Expression of 5-H1A receptors was determined by western blot analysis. Results: A depressive state was induced by stress, and treadmill exercise alleviated the depression symptoms in the stress-induced rats. Expressions of 5-HT, TPH, and HT 1A in the dorsal raphe were reduced by the induction of stress. Treadmill exercise increased 5-HT, TPH, and HT 1A expressions in the stress-induced rats. Conclusions: Treadmill exercise enhanced 5-HT synthesis through the up-regulation of 5-HT1A receptors, and improved the stress-induced depression. In the present study, treadmill exercise improved depression symptoms by enhancing 5-HT1A receptor expression. The present results suggest that treadmill exercise might be helpful for the alleviation of overactive bladder and improve sexual function. PMID:25833478

  12. 5-hydroxytryptamine1A (5-HT1A) receptor agonists: A decade of empirical evidence supports their use as an efficacious therapeutic strategy for brain trauma.

    PubMed

    Cheng, Jeffrey P; Leary, Jacob B; Sembhi, Aerin; Edwards, Clarice M; Bondi, Corina O; Kline, Anthony E

    2016-06-01

    Traumatic brain injury (TBI) is a significant and enduring health care issue with limited treatment options. While several pre-clinical therapeutic approaches have led to enhanced motor and/or cognitive performance, the benefits of these treatments have not translated to the clinic. One plausible explanation is that the therapies may not have been rigorously evaluated, thus rendering the bench-to-bedside leap premature and subsequently unsuccessful. An approach that has undergone considerable empirical research after TBI is pharmacological targeting of 5-HT1A receptors with agonists such as repinotan HCl, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), and buspirone. The goal of this review is to integrate and interpret the findings from a series of studies that evaluated the efficacy of 5-HT1A receptor agonists on functional, histological, and molecular outcome after acquired brain injury. The overwhelming consensus of this exhaustive review is that a decade of empirical evidence supports their use as an efficacious therapeutic strategy for brain trauma. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26612522

  13. Development of Plate Reader and On-Line Microfluidic Screening to Identify Ligands of the 5-Hydroxytryptamine Binding Protein in Venoms

    PubMed Central

    Otvos, Reka A.; Krishnamoorthy Iyer, Janaki; van Elk, René; Ulens, Chris; Niessen, Wilfried M. A.; Somsen, Govert W.; Kini, R. Manjunatha; Smit, August B.; Kool, Jeroen

    2015-01-01

    The 5-HT3 receptor is a ligand-gated ion channel, which is expressed in the nervous system. Its antagonists are used clinically for treatment of postoperative- and radiotherapy-induced emesis and irritable bowel syndrome. In order to better understand the structure and function of the 5-HT3 receptor, and to allow for compound screening at this receptor, recently a serotonin binding protein (5HTBP) was engineered with the Acetylcholine Binding Protein as template. In this study, a fluorescence enhancement assay for 5HTBP ligands was developed in plate-reader format and subsequently used in an on-line microfluidic format. Both assay types were validated using an existing radioligand binding assay. The on-line microfluidic assay was coupled to HPLC via a post-column split which allowed parallel coupling to a mass spectrometer to collect MS data. This high-resolution screening (HRS) system is well suitable for compound mixture analysis. As a proof of principle, the venoms of Dendroapsis polylepis, Pseudonaja affinis and Pseudonaja inframacula snakes were screened and the accurate masses of the found bioactives were established. To demonstrate the subsequent workflow towards structural identification of bioactive proteins and peptides, the partial amino acid sequence of one of the bioactives from the Pseudonaja affinis venom was determined using a bottom-up proteomics approach. PMID:26114334

  14. Participation of 5-HT1-like and 5-HT2A receptors in the contraction of human temporal artery by 5-hydroxytryptamine and related drugs.

    PubMed Central

    Verheggen, R.; Freudenthaler, S.; Meyer-Dulheuer, F.; Kaumann, A. J.

    1996-01-01

    1. We investigated the hypothesis that, as in some other large human arteries, 5-HT-induced contraction of the temporal artery is mediated through two co-existing receptor populations, 5-HT1-like- and 5-HT2A. Temporal arterial segments were obtained from patients undergoing brain surgery and rings prepared set up to contract with 5-HT and related agents. Fractions of maximal 5-HT responses mediated through 5-HT1-like and 5-HT2A receptors, f1 and f2 = 1-f1, were estimated by use of the 5-HT2A-selective antagonist ketanserin. 2. In rings with intact endothelium 5-HT evoked contractions with a -log EC50, M of 7.0. Ketanserin (10-1000 nM) antagonized part of the 5-HT-induced contractions. Ketanserin-resistant components of 5-HT-induced contractions were found with -log EC50, M of 6.9 and f1 of 0.17 (100 nM ketanserin) and -log EC50, M of 6.4 and f1 of 0.20 (1000 nM ketanserin). 3. In rings with endothelial function attenuated by enzymatic treatment, 5-HT caused contractions with a -log EC50, M of 7.2 that were partially blocked by ketanserin. Ketanserin-resistant components of 5-HT-induced contractions were found with -log EC50, M 7.4 and f1 of 0.16 (100 nM ketanserin) and -log EC50, M of 7.5 and f1 of 0.14 (1000 nM ketanserin). 4. The ketanserin-resistant component of 5-HT-evoked contraction was blocked by methiothepin (100-1000 nM) consistent with mediation through 5-HT1-like receptors. 5. In rings with intact endothelium the 5-HT1-like-selective agonist, sumatriptan, caused small contractions with a -log EC50, M of 6.5 and intrinsic activity of 0.21 with respect to 5-HT that were resistant to blockade by 1000 nM ketanserin but antagonized by 100 nM methiothepin. 6. In rings with intact endothelium the 5-HT2A receptor partial agonist SK&F 103829 (2,3,4,5-tetrahydro-8[methyl sulphonyl]-1H3-benzazepin-7-ol methensulphonate) contracted rings with a -log EC50, M of 5.0 and an intrinsic activity of 0.49 with respect to 5-HT; the effects were antagonized by ketanserin 1000 nM. 7. We conclude that 80-86% of the maximum 5-HT-evoked contraction of human temporal artery is mediated through 5-HT2A receptors, the remainder through 5-HT1-like-receptors, regardless of whether or not endothelium is functional. The 5-HT1-like-receptors are more likely to be 5-HT1D beta receptors than 5-HT1D alpha receptors and sumatriptan is a full agonist for these receptors. As found in arteries of other species, SK&F 103829 is a partial agonist for 5-HT2A receptors of human temporal artery. PMID:8789380

  15. A single channel for nitrate uptake, nitrite export and nitrite uptake by Escherichia coli NarU and a role for NirC in nitrite export and uptake.

    PubMed

    Jia, Wenjing; Tovell, Nicholas; Clegg, Stephanie; Trimmer, Mark; Cole, Jeffrey

    2009-01-01

    Two related polytopic membrane proteins of the major facilitator family, NarK and NarU, catalyse nitrate uptake, nitrite export and nitrite uptake across the Escherichia coli cytoplasmic membrane by an unknown mechanism. A 12-helix model of NarU was constructed based upon six alkaline phosphatase and beta-galactosidase fusions to NarK and the predicted hydropathy for the NarK family. Fifteen residues conserved in the NarK-NarU protein family were substituted by site-directed mutagenesis, including four residues that are essential for nitrate uptake by Aspergillus nidulans: arginines Arg(87) and Arg(303) in helices 2 and 8, and two glycines in a nitrate signature motif. Despite the wide range of substitutions studied, in no case did mutation result in loss of one biochemical function without simultaneous loss of all other functions. A NarU+ NirC+ strain grew more rapidly and accumulated nitrite more rapidly than the isogenic NarU+ NirC(-) strain. Only the NirC+ strain consumed nitrite rapidly during the later stages of growth. Under conditions in which the rate of nitrite reduction was limited by the rate of nitrite uptake, NirC+ strains reduced nitrite up to 10 times more rapidly than isogenic NarU+ strains, indicating that both nitrite efflux and nitrite uptake are largely dependent on NirC. Isotope tracer experiments with [15N]nitrate and [14N]nitrite revealed that [15N]nitrite accumulated in the extracellular medium even when there was a net rate of nitrite uptake and reduction. We propose that NarU functions as a single channel for nitrate uptake and nitrite expulsion, either as a nitrate-nitrite antiporter, or more likely as a nitrate/H+ or nitrite/H+ channel. PMID:18691156

  16. Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis

    SciTech Connect

    Lewis, P.J.; Salama, A.

    1994-10-01

    Whole-body PET scanning was performed using {sup 18}F-fluorodeoxyglucose (FDG) in two patients with hilar lymphadenopathy in whom the clinical differential diagnosis was between sarcoidosis and lymphoma. Both patients were later proven to have sarcoidosis. Uptake of {sup 18}FDG was seen in both intra- and extrathoracic lesions as well as in associated erythema nodosum. One patient underwent a repeat scan after steroid therapy where a marked decrease in hilar uptake was seen. Fluorine-18-fluorodeoxyglucose uptake is observed in lymph nodes with sarcoid involvement. Further investigation is necessary to assess if quantitative differences exist between sarcoid and malignant lymphadenopathy. 30 refs., 3 figs.

  17. Uptake of Nitrite by Neurospora crassa

    PubMed Central

    Schloemer, Robert H.; Garrett, Reginald H.

    1974-01-01

    Like the nitrate transport system, the nitrite uptake system in Neurospora crassa is induced by either nitrate or nitrite. This induction is prevented by cycloheximide, puromycin, or 6-methyl purine. The Km for nitrite of the induced nitrite uptake system is 86 μM, and the Vmax is 100 μmol of nitrite per g (wet weight) per h. Nitrite uptake is inhibited by metabolic poisons such as arsenate, dinitrophenol, cyanide, and antimycin A. No repression or inhibition of the nitrite transport system by ammonia, nitrate, or Casamino Acids was observed. PMID:4274458

  18. Thermodynamic formalism of water uptakes on solid porous adsorbents for adsorption cooling applications

    SciTech Connect

    Sun, Baichuan; Chakraborty, Anutosh

    2014-05-19

    This Letter presents a thermodynamic formulation to calculate the amount of water vapor uptakes on various adsorbents such as zeolites, metal organic frameworks, and silica gel for the development of an advanced adsorption chiller. This formalism is developed from the rigor of the partition distribution function of each water vapor adsorptive site on adsorbents and the condensation approximation of adsorptive water molecules and is validated with experimental data. An interesting and useful finding has been established that the proposed model is thermodynamically connected with the pore structures of adsorbent materials, and the water vapor uptake highly depends on the isosteric heat of adsorption at zero surface coverage and the adsorptive sites of the adsorbent materials. Employing the proposed model, the thermodynamic trends of water vapor uptakes on various adsorbents can be estimated.

  19. Sphagnum Mosses - Masters of Efficient N-Uptake while Avoiding Intoxication

    PubMed Central

    Fritz, Christian; Lamers, Leon P. M.; Riaz, Muhammad; van den Berg, Leon J. L.; Elzenga, Theo J. T. M.

    2014-01-01

    Peat forming Sphagnum mosses are able to prevent the dominance of vascular plants under ombrotrophic conditions by efficiently scavenging atmospherically deposited nitrogen (N). N-uptake kinetics of these mosses are therefore expected to play a key role in differential N availability, plant competition, and carbon sequestration in Sphagnum peatlands. The interacting effects of rain N concentration and exposure time on moss N-uptake rates are, however, poorly understood. We investigated the effects of N-concentration (1, 5, 10, 50, 100, 500 µM), N-form (15N - ammonium or nitrate) and exposure time (0.5, 2, 72 h) on uptake kinetics for Sphagnum magellanicum from a pristine bog in Patagonia (Argentina) and from a Dutch bog exposed to decades of N-pollution. Uptake rates for ammonium were higher than for nitrate, and N-binding at adsorption sites was negligible. During the first 0.5 h, N-uptake followed saturation kinetics revealing a high affinity (Km 3.5–6.5 µM). Ammonium was taken up 8 times faster than nitrate, whereas over 72 hours this was only 2 times. Uptake rates decreased drastically with increasing exposure times, which implies that many short-term N-uptake experiments in literature may well have overestimated long-term uptake rates and ecosystem retention. Sphagnum from the polluted site (i.e. long-term N exposure) showed lower uptake rates than mosses from the pristine site, indicating an adaptive response. Sphagnum therefore appears to be highly efficient in using short N pulses (e.g. rainfall in pristine areas). This strategy has important ecological and evolutionary implications: at high N input rates, the risk of N-toxicity seems to be reduced by lower uptake rates of Sphagnum, at the expense of its long-term filter capacity and related competitive advantage over vascular plants. As shown by our conceptual model, interacting effects of N-deposition and climate change (changes in rainfall) will seriously alter the functioning of Sphagnum peatlands

  20. The K+/site and H+/site stoichiometry of mitochondrial electron transport.

    PubMed

    Reynafarje, B; Lehninger, A L

    1978-09-25

    Electrode measurements of the average number of H+ ejected and K+ taken up (in the presence of valinomycin) per pair of electrons passing the energy-conserving sites of the respiratory chain of rat liver and rat heart mitochondria have given identical values of the H+/site and 5+/site ratios very close to 4 in the presence of N-ethylmaleimide, an inhibitor of interfering respiration-coupled uptake of H+ + H2PO4-. The K+/site uptake ratio of 4 not only shows that inward movement of K+ provides quantitative charge-compensation for the 4 H+ ejected, but also confirms that 4 charges are separated per pair of electrons per site. When N-ethylmaleimide is omitted, the H+/site ejection ratio is depressed, because of the interfering secondary uptake of H/+ with H2PO4- on the phosphate carrier, but the K+/site uptake ratio remains at 4.0. Addition of phosphate or acetate, which can carry H+ into respiring mitochondria, further depresses the H+/site ratio, but does not affect the K+/site ratio, which remains at 4.0. These and other considerations thus confirm our earlier stoichiometric measurements that the average H+/site ratio is 4.0 and also show that the K+/site uptake ratio can be used as a measure of the intrinsic H+/site ratio, regardless of the presence of phosphate in the medium and without the necessity of adding N-ethylmaleimide or other inhibitors of H+ + H2PO4- transport. PMID:210179

  1. Uptake of trimethoprim by renal cortex.

    PubMed

    Cacini, W; Myre, S A

    1985-10-01

    The purpose of this study was to examine the mechanisms involved in the uptake of the urinary antibacterial drug trimethoprim by incubated slices of rat renal cortex. Concentration-dependent studies of the uptake process demonstrated that a saturable component was involved. The results of inhibitor studies as well as the time-course pattern support the conclusion that at least two processes are involved in the uptake of trimethoprim. These include active transport via the organic cation system, accounting for about 40% of the total uptake, and a second component that continues to operate under conditions of inhibited cellular metabolism. Chromatographic examination of post-incubation bathing medium and slice extracts failed to demonstrate renal cortex metabolism of trimethoprim. PMID:4052093

  2. Nitrogen uptake and utilization by intact plants

    NASA Technical Reports Server (NTRS)

    Raper, C. D., Jr.; Tolley-Henry, L. C.

    1986-01-01

    The results of experiments support the proposed conceptual model that relates nitrogen uptake activity by plants as a balanced interdependence between the carbon-supplying function of the shoot and the nitrogen-supplying function of the roots. The data are being used to modify a dynamic simulation of plant growth, which presently describes carbon flows through the plant, to describe nitrogen uptake and assimilation within the plant system. Although several models have been proposed to predict nitrogen uptake and partitioning, they emphasize root characteristics affecting nutrient uptake and relay on empirical methods to describe the relationship between nitrogen and carbon flows within the plant. Researchers, on the other hand, propose to continue to attempt a mechanistic solution in which the effects of environment on nitrogen (as well as carbon) assimilation are incorporated through their direct effects on photosynthesis, respiration, and aging processes.

  3. Congo red uptake by motile Aeromonas species.

    PubMed

    Statner, B; George, W L

    1987-05-01

    Virulence of several species of enteropathogenic bacteria has been correlated with the ability of isolates to take up the dye Congo red. To determine whether Congo red uptake might be a useful marker for virulence of motile Aeromonas species, we examined 50 strains of diverse clinical origin on a medium containing 50 micrograms of Congo red per ml. All of the strains took up the dye to various degrees. For most strains, uptake was greatest at 37 degrees C and least at 22 degrees C. Production of acetyl methyl carbinol (Voges-Proskauer test) or lysine decarboxylase has been reported by some investigators to be a virulence marker for Aeromonas species. Congo red uptake did not correlate with either acetyl methyl carbinol or lysine decarboxylase production in our study. These data suggest that Congo red uptake may not be a useful marker for virulence of motile Aeromonas species. PMID:3584422

  4. CONVERGING PATTERNS OF UPTAKE AND HYDRAULIC REDISTRIBUTION OF SOIL WATER IN CONTRASTING WOODY VEGETATION TYPES

    EPA Science Inventory

    We used concurrent measurements of soil water content and soil water potential (Ysoil) to assess the effects of Ysoil on uptake and hydraulic redistribution (HR) of soil water by roots during seasonal drought cycles in six sites characterized by different types and amounts of woo...

  5. Fire effects on the mobilization and uptake of nitrogen by cheatgrass (Bromus tectorum L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cheatgrass (Bromus tectorum L.), an invasive annual grass, is displacing native species and causing increased fire frequency in the Great Basin of the southwestern United States. Growth and nitrogen uptake patterns by cheatgrass were examined in a greenhouse study using soils from sites with the sa...

  6. MACROSCOPIC APPROACHES TO ROOT WATER UPTAKE AS A FUNCTION OF WATER AND SALINITY STRESS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Computer simulation models can be important tools for analyzing and managing site-specific irrigation, soil salinization, or crop production problems. For many of these problems, computer analyses require simulations of root water uptake as a function of water and salinity stress. We give an over...

  7. Gallium-67 uptake in meningeal sarcoidosis

    SciTech Connect

    Ayres, J.G.; Hicks, B.H.; Maisey, M.N.

    1986-07-01

    A case of sarcoidosis limited to the central nervous system is described in which the diagnosis was suggested by high Ga-67 uptake in the cranial and spinal meninges. The diagnosis was confirmed by meningeal biopsy. Treatment with oral corticosteroids resulted in clinical improvement and marked reduction in Ga-67 uptake in the meninges. This is the first reported case of the central nervous system sarcoid diagnosed by Ga-67 imaging.

  8. Diaphragm and Laryngeal FDG Uptake With Hiccups.

    PubMed

    Srivastava, Madhur K; Jain, Avani S; Panneer, Venkat; Muthukrishnan, Indirani; Simon, Shelley

    2015-11-01

    F-FDG PET/CT study is a well-established investigation in diagnosis, treatment evaluation, and follow-up of malignant tumors. It is very important to know the normal biodistribution and physiologic uptake of F-FDG to prevent it from confusing as malignant disease. This article describes unusual but physiological uptake in the laryngeal and diaphragmatic muscles in a patient presenting as metastatic adenocarcinoma with unknown primary having hiccups. PMID:26204217

  9. Dependence of FDG uptake on tumor microenvironment

    SciTech Connect

    Pugachev, Andrei . E-mail: pugachea@mskcc.org; Ruan, Shutian; Carlin, Sean; Larson, Steven M.; Campa, Jose; Ling, C. Clifton; Humm, John L.

    2005-06-01

    Purpose: To investigate the factors affecting the {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) uptake in tumors at a microscopic level, by correlating it with tumor hypoxia, cellular proliferation, and blood perfusion. Methods and Materials: Nude mice bearing Dunning prostate tumors (R3327-AT) were injected with {sup 18}F-FDG and pimonidazole, bromodeoxyuridine, and, 1 min before sacrifice, with Hoechst 33342. Selected tumor sections were imaged by phosphor plate autoradiography, while adjacent sections were used to obtain the images of the spatial distribution of Hoechst 33342, pimonidazole, and bromodeoxyuridine. The images were co-registered and analyzed on a pixel-by-pixel basis. Results: Statistical analysis of the data obtained from these tumors demonstrated that {sup 18}F-FDG uptake was positively correlated with pimonidazole staining intensity in each data set studied. Correlation of FDG uptake with bromodeoxyuridine staining intensity was always negative. In addition, FDG uptake was always negatively correlated with the staining intensity of Hoechst 33342. Conclusions: For the Dunning prostate tumors studied, FDG uptake was always positively correlated with hypoxia and negatively correlated with both cellular proliferation and blood flow. Therefore, for the tumor model studied, higher FDG uptake is indicative of tumor hypoxia, but neither blood flow nor cellular proliferation.

  10. Endocytosis of the major yolk proteins of the silkmoth, Hyalophora cecropia: Uptake kinetics and interactions

    SciTech Connect

    Kulakosky, P.C.

    1989-01-01

    The oocytes of Lepidopteran insects take up several yolk proteins in defined proportions even though their relative availability in the hemolymph changes during the several days required to complete yolk formation in all the eggs. There are three hemolymph yolk precursors, vitellogenin, microvitellogenin and lipophorin; one precursor, paravitellogenin is produced in the ovary. The control mechanism for their proportional endocytosis is not known. In this thesis, the author describe the purification of all four proteins and the radiolabeling of the hemolymph precursors. The radiolabeled proteins were tested with an in vitro incubation system to assess the biological activity of the proteins and the reliability of the incubation methods. All of the labeled probes were transferred from the incubation medium to yolk spheres within the oocyte in a saturable, energy-dependent, and stage-specific manner. The rates of uptake were similar to the estimated rates of uptake in situ. The concentration dependence of in vitro uptake was investigated and found to be consistent with in situ concentrations and the composition of yolk in mature eggs. Two precursors, vitellogenin and lipophorin, competed for uptake indicating that they share a common binding site while the third, microvitellin, did not compete with the others. Though vitellogenin and lipophorin competed for uptake, only vitellogenin displayed the unique ability to increase the uptake rate of microvitellin and fluid in vitro.

  11. Caged mussels and semipermeable membrane devices as indicators of organic contaminant uptake in Dorchester and Duxbury Bays, Massachusetts

    SciTech Connect

    Peven, C.S.; Uhler, A.D.; Querzoli, F.J.

    1996-02-01

    An experiment to measure organic contaminant depuration by the blue mussel (Mytilus edulis) was carried out by transplanting mussels in stainless steel cages from a known contaminated site in Dorchester Bay, Massachusetts to a documented clean site in Duxbury Bay, Massachusetts approximately 30 nmi south of the original collection site. A parallel contaminant uptake experiment was performed in which mussels from Duxbury Bay were collected and deployed in similar cages in Dorchester Bay. The bivalves were collected from each transplant site at set intervals over a period of 95 days to monitor the rates and selectivity of depuration and uptake, respectively, of polynuclear atomic hydrocarbons (PAH), polychlorinated biphenyls (PCB), and chlorinated pesticides. In a related study, semipermeable membrane devices (SPMD: polyethylene bags) containing the lipid material triolein were deployed in Dorchester Bay and collected at the same frequency as the caged mussels to evaluate their effectiveness as models for estimating bioconcentration of target organic contaminants. At the Duxbury site, results suggest that the caged mussels depurated contaminants within 68 days to levels found in native animals at the site. At the Dorchester site, bivalves concentrated the contaminants to a level similar to the native M. edulis. PCB and DDT uptake rates were found to be similar between caged mussels and SPMDs; PAH uptake by the SPMDs was initially lower than by transplanted bivalves. PCB and PAH assemblages were noticeably different between bivalves and SPMDs deployed at the same site.

  12. In vivo radiometric analysis of glucose uptake and distribution in mouse bone

    PubMed Central

    Zoch, Meredith L; Abou, Diane S; Clemens, Thomas L; Thorek, Daniel L J; Riddle, Ryan C

    2016-01-01

    Bone formation and remodeling occurs throughout life and requires the sustained activity of osteoblasts and osteoclasts, particularly during periods of rapid bone growth. Despite increasing evidence linking bone cell activity to global energy homeostasis, little is known about the relative energy requirements or substrate utilization of bone cells. In these studies, we measured the uptake and distribution of glucose in the skeleton in vivo using positron-emitting 18F-fluorodeoxyglucose ([18F]-FDG) and non-invasive, high-resolution positron emission tomography/computed tomography (PET/CT) imaging and ex vivo autoradiography. Assessment of [18F]-FDG uptake demonstrated that relative to other tissues bone accumulated a significant fraction of the total dose of the glucose analog. Skeletal accumulation was greatest in young mice undergoing the rapid bone formation that characterizes early development. PET/CT imaging revealed that [18F]-FDG uptake was greatest in the epiphyseal and metaphyseal regions of long bones, which accords with the increased osteoblast numbers and activity at this skeletal site. Insulin administration significantly increased skeletal accumulation of [18F]-FDG, while uptake was reduced in mice lacking the insulin receptor specifically in osteoblasts or fed a high-fat diet. Our results indicated that the skeleton is a site of significant glucose uptake and that its consumption by bone cells is subject to regulation by insulin and disturbances in whole-body metabolism. PMID:27088042

  13. In vivo radiometric analysis of glucose uptake and distribution in mouse bone.

    PubMed

    Zoch, Meredith L; Abou, Diane S; Clemens, Thomas L; Thorek, Daniel L J; Riddle, Ryan C

    2016-01-01

    Bone formation and remodeling occurs throughout life and requires the sustained activity of osteoblasts and osteoclasts, particularly during periods of rapid bone growth. Despite increasing evidence linking bone cell activity to global energy homeostasis, little is known about the relative energy requirements or substrate utilization of bone cells. In these studies, we measured the uptake and distribution of glucose in the skeleton in vivo using positron-emitting (18)F-fluorodeoxyglucose ([(18)F]-FDG) and non-invasive, high-resolution positron emission tomography/computed tomography (PET/CT) imaging and ex vivo autoradiography. Assessment of [(18)F]-FDG uptake demonstrated that relative to other tissues bone accumulated a significant fraction of the total dose of the glucose analog. Skeletal accumulation was greatest in young mice undergoing the rapid bone formation that characterizes early development. PET/CT imaging revealed that [(18)F]-FDG uptake was greatest in the epiphyseal and metaphyseal regions of long bones, which accords with the increased osteoblast numbers and activity at this skeletal site. Insulin administration significantly increased skeletal accumulation of [(18)F]-FDG, while uptake was reduced in mice lacking the insulin receptor specifically in osteoblasts or fed a high-fat diet. Our results indicated that the skeleton is a site of significant glucose uptake and that its consumption by bone cells is subject to regulation by insulin and disturbances in whole-body metabolism. PMID:27088042

  14. Nonreductive Iron Uptake Mechanism in the Marine Alveolate Chromera velia1[W

    PubMed Central

    Sutak, Robert; Šlapeta, Jan; San Roman, Mabel; Camadro, Jean-Michel; Lesuisse, Emmanuel

    2010-01-01

    Chromera velia is a newly cultured photosynthetic marine alveolate. This microalga has a high iron requirement for respiration and photosynthesis, although its natural environment contains less than 1 nm of this metal. We found that this organism uses a novel mechanism of iron uptake, differing from the classic reductive and siderophore-mediated iron uptake systems characterized in the model yeast Saccharomyces cerevisiae and present in most yeasts and terrestrial plants. C. velia has no trans-plasma membrane electron transfer system, and thus cannot reduce extracellular ferric chelates. It is also unable to use hydroxamate siderophores as iron sources. Iron uptake from ferric citrate by C. velia is not inhibited by a ferrous chelator, but the rate of uptake is strongly decreased by increasing the ferric ligand (citrate) concentration. The cell wall contains a large number of iron binding sites, allowing the cells to concentrate iron in the vicinity of the transport sites. We describe a model of iron uptake in which aqueous ferric ions are first concentrated in the cell wall before being taken up by the cells without prior reduction. We discuss our results in relation to the strategies used by the phytoplankton to take up iron in the oceans. PMID:20724644

  15. Utilization of a Model for Uptake of Cadmium by Plants as a Phytoremediation Assessment Tool

    NASA Astrophysics Data System (ADS)

    Takahashi, M.; Furbish, D. J.; Clarke, J.

    2008-12-01

    Some traditional methods of environmental remediation, such as removal and disposal of contaminated soil, are loosing economic favor and public acceptance, while others, such as in situ phytoremediation, are being carefully examined because of their attractiveness as environmentally friendly, low-cost solutions to site clean-up. The success of phytoremediation strategies, however, hinges on the ability of selected plants, or plant communities, to effectively uptake, accumulate and tolerate targeted contaminants. Heavy metals, specifically cadmium (Cd), are not essential nutrients to plants. However, chemically similar zinc (Zn) is a micronutrient and is actively taken up by hyperaccumulators. For this reason, the mechanisms involved in uptake of Cd parallel those of Zn. Ideally, Cd would be allocated to the stem, leaf, and/or flower, where it becomes harvestable. Our modeling work simulates the uptake and the storage of Cd in a growing hyperaccumulator. After uptake, Cd is partitioned between adsorption to plant tissue and upward movement to leaves driven by transpiration. Uptake, adsorption and transport are also regulated by phytotoxicity. Simulations suggest that a young plant with small biomass can quickly reach phytotoxicity, which shuts down the normal operation of the plant. Conversely, mature plants on a mildly contaminated site, if harvested before the plants die due to phytotoxicity or natural cause, not only survive but may occasionally thrive. The immediate aim is to estimate the effectiveness and limitations of Cd uptake by hyperaccumulators. The eventual goal of this study is to expand the model in spatial and temporal scales, from individual plants to the community scale, and from one harvest interval to several generations. Understanding the interface between physical and biological processes, specifically the uptake and release of contaminants, provides scientists and engineers tools to assess whether phytoremediation is a reasonable strategy for a

  16. Relating phosphorus uptake to changes in transient storage and streambed sediment characteristics in headwater tributaries of Valley Creek, an urbanizing watershed

    NASA Astrophysics Data System (ADS)

    Ryan, Robert J.; Packman, Aaron I.; Kilham, Susan S.

    2007-04-01

    SummaryPhosphorus uptake dynamics were examined in two small streams in the Valley Creek watershed, located in an urbanizing area approximately 30 km west of Philadelphia, Pennsylvania, USA. The goal of this research was to examine how phosphorus uptake is influenced by temporal changes in bed sediment characteristics and transient storage in streams within an urbanizing watershed. We conducted tracer studies with a conservative solute, observed phosphorus uptake in situ and in laboratory experiments, and measured fine bed sediment grain size distributions and chemical compositions at both sites. At the Morehall Rd. site, the total laboratory and in situ uptake rates were related to the silt-clay ( d < 50 μm) content of the fine ( d < 2 mm) bed sediment and the sediment phosphorus concentration. The in situ uptake rate was also related to the sediment magnesium content and the transient storage exchange rate and area. At the Sheldrake Rd. site, the phosphorus uptake rates observed in situ and in the laboratory were not significantly related to any of the measured stream or sediment characteristics. However, the areal average uptake (uptake flux), was related to the transient storage exchange rate. In addition, the abiotic contribution to in situ uptake was evaluated by comparing the in situ and laboratory measured uptake rates. The total abiotic in situ uptake rate was found to be related to the bed sediment silt-clay content and the transient storage residence time, while the abiotic uptake flux was related to the transient storage residence time. Overall, these urbanizing streams were less efficient at removing phosphorus from the water column than forested streams in non-urban settings.

  17. Eco-Hydro-Connectivity: Tracking the Diurnal Signal of Plant Water Uptake through the Hydrologic System

    NASA Astrophysics Data System (ADS)

    Blume, T.; Hassler, S. K.; Heidbuechel, I.; Simard, S.; Guntner, A.; Weiler, M.

    2014-12-01

    Plant water uptake during summer is characterized by strong diurnal fluctuations. As a result a diurnal sink term is imposed on catchment storage, affecting the unsaturated zone, sometimes the saturated zone and even streamflow. Detecting this signal and understanding its propagation through the hydrological system may help to better quantify eco-hydrological connectivity. The extent and strength of the propagation of this signal from plant to soil to ground- and streamwater was investigated with a unique setup of 46 field sites in Luxemburg and 15 field sites in Germany. These sites cover a range of geologies, soils, topographies and types of vegetation. Vegetation types include grassland, pine forest (young and old) and different deciduous forest stands. Available data at all sites includes information at high temporal resolution from 3-5 soil moisture profiles, matrix potential, piezometers and sapflow sensors (as proxy for plant water uptake) as well as standard climate data. At sites with access to a stream, discharge or water level is also recorded. Signal strength (amplitude of diurnal fluctuations) can thus be traced through the system and gives an indication of the physical sphere of influence of plant water uptake i.e. the "eco-hydro-connectivity". The analysis of time lags (or phase shifts) between daily fluctuations in temperature, radiation, sapflow, soil water, groundwater and streamflow gives further insights into the processes driving and propagating these signals and inter-site comparison allows for the investigation of local controls.

  18. Brain uptake, retention, and efflux of aluminum and manganese.

    PubMed Central

    Yokel, Robert A

    2002-01-01

    My colleagues and I investigated the sites and mechanisms of aluminum (Al) and manganese (Mn) distribution through the blood-brain barrier (BBB). Microdialysis was used to sample non-protein-bound Al in the extracellular fluid (ECF) of blood (plasma) and brain. Brain ECF Al appearance after intravenous Al citrate injection was too rapid to attribute to diffusion or to transferrin-receptor-mediated endocytosis, suggesting another carrier-mediated process. The brain:blood ECF Al concentration ratio was 0.15 at constant blood and brain ECF Al concentrations, suggesting carrier-mediated brain Al efflux. Pharmacological manipulations suggested the efflux carrier might be a monocarboxylate transporter (MCT). However, the lack of Al (14)C-citrate uptake into rat erythrocytes suggested it is not a good substrate for isoform MCT1 or for the band 3 anion exchanger. Al (14)C-citrate uptake into murine-derived brain endothelial cells appeared to be carrier mediated, Na independent, pH independent, and energy dependent. Uptake was inhibited by substrate/inhibitors of the MCT and organic anion transporter families. Determination of (26)Al in rat brain at various times after intravenous (26)Al suggested a prolonged brain (26)Al half-life. It appears that Al transferrin and Al citrate cross the BBB by different mechanisms, that much of the Al entering brain ECF is rapidly effluxed, probably as Al citrate, but that some Al is retained for quite some time. Brain influx of the Mn(2+) ion and Mn citrate, determined with the in situ brain perfusion technique, was greater than that attributable to diffusion, suggesting carrier-mediated uptake. Mn citrate uptake was approximately 3-fold greater than the Mn(2+) ion, suggesting it is a primary Mn species entering the brain. After Mn(2+) ion, Mn citrate, or Mn transferrin injection into the brain, brain Mn efflux was not more rapid than that predicted from diffusion. The BBB permeation of Al and Mn is mediated by carriers that may help

  19. Examination of the mechanism of action of nitrogen monoxide on iron uptake from transferrin.

    PubMed

    Watts, R N; Richardson, D R

    2000-08-01

    Nitrogen monoxide (NO) exerts many of its functions by binding to iron (Fe) in the active sites of a number of key proteins. Previously we have shown that NO produced by NO-generating agents decreased cellular Fe uptake from transferrin (Tf). However, the mechanism of this effect was not elucidated. In this study we examined the possible mechanisms whereby NO could interfere with Fe uptake. Our experiments demonstrate that NO produced by the NO generator S-nitroso-N-acetylpenicillamine was slightly more effective than the Fe chelator deferoxamine at reducing iron 59 uptake from 59Fe-labeled Tf by LMTK- fibroblasts. Other NO generators including S-nitrosoglutathione (GSNO) and spermine-NONOate also decreased 59Fe uptake from 59Fe-labeled Tf. In contrast, precursors of these compounds that do not release NO had no effect. When the RAW264.7 macrophage cell line was activated to produce NO by incubation with lipopolysaccharide or lipopolysaccharide and interferon-gamma, a decrease in 59Fe uptake from 59Fe-labeled Tf was also observed. Experiments with electron paramagnetic resonance spectroscopy and ultraviolet-Vis spectrophotometry demonstrated that NO did not prevent Fe uptake by binding to the Fe-ligating sites of Tf, suggesting that it acted more distally. Because the uptake of Fe is an energy-dependent process, and since NO inhibits mitochondrial respiration, cellular adenosine triphosphate (ATP) was estimated after incubation with GSNO. In the presence of D-glucose (D-G), GSNO reduced ATP levels by 35% as compared with the control, while in the absence of D-G, GSNO reduced ATP by 72%. When the same experiments were performed with D-fructose (D-F), which cannot be efficiently metabolized by fibroblasts, no "rescue" effect was observed on ATP levels. The addition of D-G to GSNO prevented the decrease in 59Fe uptake from 59Fe-labeled Tf while D-F did not, in good correlation with their effects on ATP levels. These results suggest that D-G acts as a salvage

  20. Selenium Uptake and Volatilization by Marine Algae

    NASA Astrophysics Data System (ADS)

    Luxem, Katja E.; Vriens, Bas; Wagner, Bettina; Behra, Renata; Winkel, Lenny H. E.

    2015-04-01

    Selenium (Se) is an essential trace nutrient for humans. An estimated one half to one billion people worldwide suffer from Se deficiency, which is due to low concentrations and bioavailability of Se in soils where crops are grown. It has been hypothesized that more than half of the atmospheric Se deposition to soils is derived from the marine system, where microorganisms methylate and volatilize Se. Based on model results from the late 1980s, the atmospheric flux of these biogenic volatile Se compounds is around 9 Gt/year, with two thirds coming from the marine biosphere. Algae, fungi, and bacteria are known to methylate Se. Although algal Se uptake, metabolism, and methylation influence the speciation and bioavailability of Se in the oceans, these processes have not been quantified under environmentally relevant conditions and are likely to differ among organisms. Therefore, we are investigating the uptake and methylation of the two main inorganic Se species (selenate and selenite) by three globally relevant microalgae: Phaeocystis globosa, the coccolithophorid Emiliania huxleyi, and the diatom Thalassiosira oceanica. Selenium uptake and methylation were quantified in a batch experiment, where parallel gas-tight microcosms in a climate chamber were coupled to a gas-trapping system. For E. huxleyi, selenite uptake was strongly dependent on aqueous phosphate concentrations, which agrees with prior evidence that selenite uptake by phosphate transporters is a significant Se source for marine algae. Selenate uptake was much lower than selenite uptake. The most important volatile Se compounds produced were dimethyl selenide, dimethyl diselenide, and dimethyl selenyl sulfide. Production rates of volatile Se species were larger with increasing intracellular Se concentration and in the decline phase of the alga. Similar experiments are being carried out with P. globosa and T. oceanica. Our results indicate that marine algae are important for the global cycling of Se

  1. Physiological metal uptake by Nostoc punctiforme.

    PubMed

    Hudek, L; Rai, S; Michalczyk, A; Rai, L C; Neilan, B A; Ackland, M Leigh

    2012-10-01

    Trace metals are required for many cellular processes. The acquisition of trace elements from the environment includes a rapid adsorption of metals to the cell surface, followed by a slower internalization. We investigated the uptake of the trace elements Co(2+), Cu(2+), Mn(2+), Ni(2+), and Zn(2+) and the non-essential divalent cation Cd(2+) in the cyanobacterium Nostoc punctiforme. For each metal, a dose response study based on cell viability showed that the highest non-toxic concentrations were: 0.5 μM Cd(2+), 2 μM Co(2+), 0.5 μM Cu(2+), 500 μM Mn(2+), 1 μM Ni(2+), and 18 μM Zn(2+). Cells exposed to these non-toxic concentrations with combinations of Zn(2+) and Cd(2+), Zn(2+) and Co(2+), Zn(2+) and Cu(2+) or Zn(2+) and Ni(2+), had reduced growth in comparison to controls. Cells exposed to metal combinations with the addition of 500 μM Mn(2+) showed similar growth compared to the untreated controls. Metal levels were measured after one and 72 h for whole cells and absorbed (EDTA-resistant) fractions and used to calculate differential uptake rates for each metal. The differences in binding and internalisation between different metals indicate different uptake processes exist for each metal. For each metal, competitive uptake experiments using (65)Zn showed that after 72 h of exposure Zn(2+) uptake was reduced by most metals particularly 0.5 μM Cd(2+), while 2 μM Co(2+) increased Zn(2+) uptake. This study demonstrates that N. punctiforme discriminates between different metals and favourably substitutes their uptake to avoid the toxic effects of particular metals. PMID:22592442

  2. Vimentin mediates uptake of C3 exoenzyme.

    PubMed

    Rohrbeck, Astrid; Schröder, Anke; Hagemann, Sandra; Pich, Andreas; Höltje, Markus; Ahnert-Hilger, Gudrun; Just, Ingo

    2014-01-01

    Clostridium botulinum C3 exoenzyme (C3) selectively inactivates RhoA/B/C GTPases by ADP-ribosylation. Based on this substrate specificity C3 is a well-established tool in cell biology. C3 is taken up by eukaryotic cells although lacking an uptake and translocation domain. Based on different approaches vimentin was identified as membranous C3-interaction partner by mass spectrometry. Vimentin in fact was partly localized at the outer surface of hippocampal HT22 cells and J744A.1 macrophages. Domain analysis identified the rod domain as binding partner of C3. Vimentin was also involved in uptake of C3 as shown by knock down of vimentin in HT22 and J774A.1 cells. The involvement of vimentin in uptake of C3 was further supported by the findings that the vimentin disruptor acrylamide blocked uptake of C3. Vimentin is not only a major organizing element of the intermediate filament network but is also involved in both binding and uptake of C3 exoenzyme. PMID:24967582

  3. Effect of morphine on synaptosomal Ca++ uptake.

    PubMed

    Guerrero-Munoz, F; Cerreta, K V; Guerrero, M L; Way, E L

    1979-04-01

    The effect of morphine on the uptake of 45Ca++ was studied in synaptosomes from mouse brain using two procedures, centrifugation and filtration. The addition of morphine (1.7 x 10(-7) or 3.4 x 10(-7) M) reduced 45CA++ uptake by either technique, although the basal 45Ca++ uptake by the filtration method was approximately 7-fold higher than that by the centrifugation procedure. Similar effects were obtained after acute morphine treatment with 10 mg/kg s.c. Previous naloxone in vitro treatment (1.9 x 10(-8) M) or in vivo administration (2 mg/kg s.c.) reversed the morphine inhibition of the 45Ca++ uptake. On the other hand, after the animal was rendered tolerant and dependent by morphine pellet implantation, an enhancement of the synaptosomal 45Ca++ uptake was observed. It is concluded that changes in Ca++ fluxes in synaptosomes observed after acute and chronic morphine treatment may be involved with morphine pharmacological action related with analgesia, tolerance and physical dependence. PMID:571016

  4. Fluoride uptake by Streptococcus mutans 6715.

    PubMed Central

    Whitford, G M; Schuster, G S; Pashley, D H; Venkateswarlu, P

    1977-01-01

    The short-term kinetics of fluoride uptake by cells from 20- to 22-h cultures of Streptococcus mutans strain 6715 were studied using rapid filtration and centrifugation techniques. Saline-suspended organisms were diluted with fluoride-containing solutions buffered at four different pH values (2.0, 4.0, 5.5, and 8.2). Fluoride disappearance from the medium was inversely related to pH and to the duration of the exposure at any given pH. The uptake was rapid and extensive at the lower pH values and decreased as the pH increased. Media fluoride concentrations subsequently increased; i.e., fluoride was released from the cells. The presence of glucose, cyanide, or iodoacetate did not influence the results. However, preincubation of the cells in fluoride-free buffers, followed by the addition of fluoride, reduced fluoride uptake markedly. Cell-to-media pH gradients were determined by the distribution of 14C-labeled 5,5-dimethyl-2,4-oxazolidinedione. Fluoride uptake was found to be a function of the magnitude of the pH gradient (P less than 0.001). It is hypothesized that fluoride uptake occurs by the diffusion of hydrogen fluoride and the subsequent trapping of ionic fluoride. PMID:22490

  5. The Uptake of GABA in Trypanosoma cruzi.

    PubMed

    Galvez Rojas, Robert L; Ahn, Il-Young; Suárez Mantilla, Brian; Sant'Anna, Celso; Pral, Elizabeth Mieko Furusho; Silber, Ariel Mariano

    2015-01-01

    Gamma aminobutyric acid (GABA) is widely known as a neurotransmitter and signal transduction molecule found in vertebrates, plants, and some protozoan organisms. However, the presence of GABA and its role in trypanosomatids is unknown. Here, we report the presence of intracellular GABA and the biochemical characterization of its uptake in Trypanosoma cruzi, the etiological agent of Chagas' disease. Kinetic parameters indicated that GABA is taken up by a single transport system in pathogenic and nonpathogenic forms. Temperature dependence assays showed a profile similar to glutamate transport, but the effect of extracellular cations Na(+) , K(+) , and H(+) on GABA uptake differed, suggesting a different uptake mechanism. In contrast to reports for other amino acid transporters in T. cruzi, GABA uptake was Na(+) dependent and increased with pH, with a maximum activity at pH 8.5. The sensitivity to oligomycin showed that GABA uptake is dependent on ATP synthesis. These data point to a secondary active Na(+) /GABA symporter energized by Na(+) -exporting ATPase. Finally, we show that GABA occurs in the parasite's cytoplasm under normal culture conditions, indicating that it is regularly taken up from the culture medium or synthesized through an still undescribed metabolic pathway. PMID:25851259

  6. Explanatory Variance in Maximal Oxygen Uptake

    PubMed Central

    Robert McComb, Jacalyn J.; Roh, Daesung; Williams, James S.

    2006-01-01

    The purpose of this study was to develop a prediction equation that could be used to estimate maximal oxygen uptake (VO2max) from a submaximal water running protocol. Thirty-two volunteers (n =19 males, n = 13 females), ages 18 - 24 years, underwent the following testing procedures: (a) a 7-site skin fold assessment; (b) a land VO2max running treadmill test; and (c) a 6 min water running test. For the water running submaximal protocol, the participants were fitted with an Aqua Jogger Classic Uni-Sex Belt and a Polar Heart Rate Monitor; the participants’ head, shoulders, hips and feet were vertically aligned, using a modified running/bicycle motion. A regression model was used to predict VO2max. The criterion variable, VO2max, was measured using open-circuit calorimetry utilizing the Bruce Treadmill Protocol. Predictor variables included in the model were percent body fat (% BF), height, weight, gender, and heart rate following a 6 min water running protocol. Percent body fat accounted for 76% (r = -0.87, SEE = 3.27) of the variance in VO2max. No other variables significantly contributed to the explained variance in VO2max. The equation for the estimation of VO2max is as follows: VO2max ml.kg-1·min-1 = 56.14 - 0.92 (% BF). Key Points Body Fat is an important predictor of VO2 max. Individuals with low skill level in water running may shorten their stride length to avoid the onset of fatigue at higher work-loads, therefore, the net oxygen cost of the exercise cannot be controlled in inexperienced individuals in water running at fatiguing workloads. Experiments using water running protocols to predict VO2max should use individuals trained in the mechanics of water running. A submaximal water running protocol is needed in the research literature for individuals trained in the mechanics of water running, given the popularity of water running rehabilitative exercise programs and training programs. PMID:24260003

  7. Reactive uptake of trace metals in the hyporheic zone of a mining- contaminated stream, Pinal Creek, Arizona

    USGS Publications Warehouse

    Fuller, C.C.; Harvey, J.W.

    2000-01-01

    Significant uptake of dissolved metals occurred by interaction of groundwater and surface water with hyporheic-zone sediments during transport in Pinal Creek, AZ. The extent of trace metal uptake was calculated by mass balance measurements made directly within the hyporheic zone. A conservative solute tracer injected into the stream was used to quantify hydrologic exchange with the stream and groundwater. Fractional reactive uptake of dissolved metals entering the hyporheic zone was determined at 29 sites and averaged 52 ?? 25, 27 ?? 19, and 36 ?? 24% for Co, Ni, and Zn, compared with Mn uptake of 22 ?? 19%. First-order rate constants (??(h)) of metal uptake in the hyporheic zone were determined at seven sites using the exchange rate of water derived from tracer arrival in the streambed. Reaction-time constants (1/??(h)) averaged 0.41, 0.84, and 0.38 h for Co, Ni, and Zn, respectively, and 1.3 h for Mn. In laboratory experiments with streambed sediments, metal uptake increased with preexisting Mn oxide concentration, supporting our interpretation that Mn oxides in the hyporheic zone enhance trace metal uptake. Reach-scale mass-balance calculations that include groundwater metal inputs indicated that decreases in metal loads ranged from 12 to 68% over the 7-km perennial reach depending on the metal. The decreases in metal loads are attributed to uptake of trace metals by Mn oxides in the hyporheic zone that is enhanced because of ongoing Mn oxide formation. Analysis of dissolved- metal streambed profiles and conservative solute tracers provide a valuable tool for quantifying metal uptake or release in the hyporheic zone of contaminated streams.

  8. Characterization of a Dipartite Iron Uptake System from Uropathogenic Escherichia coli Strain F11*

    PubMed Central

    Koch, Doreen; Chan, Anson C. K.; Murphy, Michael E. P.; Lilie, Hauke; Grass, Gregor; Nies, Dietrich H.

    2011-01-01

    In the uropathogenic Escherichia coli strain F11, in silico genome analysis revealed the dicistronic iron uptake operon fetMP, which is under iron-regulated control mediated by the Fur regulator. The expression of fetMP in a mutant strain lacking known iron uptake systems improved growth under iron depletion and increased cellular iron accumulation. FetM is a member of the iron/lead transporter superfamily and is essential for iron uptake by the Fet system. FetP is a periplasmic protein that enhanced iron uptake by FetM. Recombinant FetP bound Cu(II) and the iron analog Mn(II) at distinct sites. The crystal structure of the FetP dimer reveals a copper site in each FetP subunit that adopts two conformations: CuA with a tetrahedral geometry composed of His44, Met90, His97, and His127, and CuB, a second degenerate octahedral geometry with the addition of Glu46. The copper ions of each site occupy distinct positions and are separated by ∼1.3 Å. Nearby, a putative additional Cu(I) binding site is proposed as an electron source that may function with CuA/CuB displacement to reduce Fe(III) for transport by FetM. Together, these data indicate that FetMP is an additional iron uptake system composed of a putative iron permease and an iron-scavenging and potentially iron-reducing periplasmic protein. PMID:21596746

  9. Potassium Uptake Modulates Staphylococcus aureus Metabolism.

    PubMed

    Gries, Casey M; Sadykov, Marat R; Bulock, Logan L; Chaudhari, Sujata S; Thomas, Vinai C; Bose, Jeffrey L; Bayles, Kenneth W

    2016-01-01

    As a leading cause of community-associated and nosocomial infections, Staphylococcus aureus requires sophisticated mechanisms that function to maintain cellular homeostasis in response to its exposure to changing environmental conditions. The adaptation to stress and maintenance of homeostasis depend largely on membrane activity, including supporting electrochemical gradients and synthesis of ATP. This is largely achieved through potassium (K(+)) transport, which plays an essential role in maintaining chemiosmotic homeostasis, affects antimicrobial resistance, and contributes to fitness in vivo. Here, we report that S. aureus Ktr-mediated K(+) uptake is necessary for maintaining cytoplasmic pH and the establishment of a proton motive force. Metabolite analyses revealed that K(+) deficiency affects both metabolic and energy states of S. aureus by impairing oxidative phosphorylation and directing carbon flux toward substrate-level phosphorylation. Taken together, these results underline the importance of K(+) uptake in maintaining essential components of S. aureus metabolism. IMPORTANCE Previous studies describing mechanisms for K(+) uptake in S. aureus revealed that the Ktr-mediated K(+) transport system was required for normal growth under alkaline conditions but not under neutral or acidic conditions. This work focuses on the effect of K(+) uptake on S. aureus metabolism, including intracellular pH and carbon flux, and is the first to utilize a pH-dependent green fluorescent protein (GFP) to measure S. aureus cytoplasmic pH. These studies highlight the role of K(+) uptake in supporting proton efflux under alkaline conditions and uncover a critical role for K(+) uptake in establishing efficient carbon utilization. PMID:27340697

  10. Potassium Uptake Modulates Staphylococcus aureus Metabolism

    PubMed Central

    Gries, Casey M.; Sadykov, Marat R.; Bulock, Logan L.; Chaudhari, Sujata S.; Thomas, Vinai C.; Bose, Jeffrey L.

    2016-01-01

    ABSTRACT As a leading cause of community-associated and nosocomial infections, Staphylococcus aureus requires sophisticated mechanisms that function to maintain cellular homeostasis in response to its exposure to changing environmental conditions. The adaptation to stress and maintenance of homeostasis depend largely on membrane activity, including supporting electrochemical gradients and synthesis of ATP. This is largely achieved through potassium (K+) transport, which plays an essential role in maintaining chemiosmotic homeostasis, affects antimicrobial resistance, and contributes to fitness in vivo. Here, we report that S. aureus Ktr-mediated K+ uptake is necessary for maintaining cytoplasmic pH and the establishment of a proton motive force. Metabolite analyses revealed that K+ deficiency affects both metabolic and energy states of S. aureus by impairing oxidative phosphorylation and directing carbon flux toward substrate-level phosphorylation. Taken together, these results underline the importance of K+ uptake in maintaining essential components of S. aureus metabolism. IMPORTANCE Previous studies describing mechanisms for K+ uptake in S. aureus revealed that the Ktr-mediated K+ transport system was required for normal growth under alkaline conditions but not under neutral or acidic conditions. This work focuses on the effect of K+ uptake on S. aureus metabolism, including intracellular pH and carbon flux, and is the first to utilize a pH-dependent green fluorescent protein (GFP) to measure S. aureus cytoplasmic pH. These studies highlight the role of K+ uptake in supporting proton efflux under alkaline conditions and uncover a critical role for K+ uptake in establishing efficient carbon utilization. PMID:27340697

  11. Tracking the diurnal signal of plant water uptake through the hydrologic system

    NASA Astrophysics Data System (ADS)

    Blume, Theresa; Hassler, Sibylle; Heidbüchel, Ingo; Weiler, Markus; Simard, Sonia; Güntner, Andreas; Heinrich, Ingo

    2015-04-01

    Plant water uptake during summer is characterized by strong diurnal fluctuations. As a result a diurnal sink term is imposed on catchment storage, affecting the unsaturated zone, sometimes the saturated zone and even streamflow. Detecting this signal and understanding its propagation through the hydrological system may help to better quantify eco-hydrological connectivity. The extent and strength of the propagation of this signal from plant to soil to ground- and stream water was investigated with a unique setup of 46 field sites in Luxemburg and 15 field sites in Germany. These sites cover a range of geologies, soils, topographies and types of vegetation. Vegetation types include grassland, pine forest (young and old) and different deciduous forest stands. Available data at all sites includes information at high temporal resolution from 3-5 soil moisture profiles, matrix potential, piezometers and sapflow sensors (as proxy for plant water uptake) as well as standard climate data. At sites with access to a stream, discharge or water level is also recorded. Signal strength (amplitude of diurnal fluctuations) can thus be traced through the system and gives an indication of the physical sphere of influence of plant water uptake i.e. the "eco-hydro-connectivity". Temporal dynamics of signal strength furthermore suggest a shifting spatial distribution of root water uptake with time. The analysis of time lags (or phase shifts) between daily fluctuations in temperature, radiation, sapflow, soil water, groundwater and streamflow gives further insights into the processes driving and propagating these signals and inter-site comparison allows for the investigation of local controls.

  12. Blood flow and oxygen uptake during exercise

    NASA Technical Reports Server (NTRS)

    Mitchell, J. W.; Stolwijk, J. A. J.; Nadel, E. R.

    1973-01-01

    A model is developed for predicting oxygen uptake, muscle blood flow, and blood chemistry changes under exercise conditions. In this model, the working muscle mass system is analyzed. The conservation of matter principle is applied to the oxygen in a unit mass of working muscle under transient exercise conditions. This principle is used to relate the inflow of oxygen carried with the blood to the outflow carried with blood, the rate of change of oxygen stored in the muscle myoglobin, and the uptake by the muscle. Standard blood chemistry relations are incorporated to evaluate venous levels of oxygen, pH, and carbon dioxide.

  13. Enantioselective cellular uptake of chiral semiconductor nanocrystals

    NASA Astrophysics Data System (ADS)

    Martynenko, I. V.; Kuznetsova, V. A.; Litvinov, I. K.; Orlova, A. O.; Maslov, V. G.; Fedorov, A. V.; Dubavik, A.; Purcell-Milton, F.; Gun'ko, Yu K.; Baranov, A. V.

    2016-02-01

    The influence of the chirality of semiconductor nanocrystals, CdSe/ZnS quantum dots (QDs) capped with L- and D-cysteine, on the efficiency of their uptake by living Ehrlich Ascite carcinoma cells is studied by spectral- and time-resolved fluorescence microspectroscopy. We report an evident enantioselective process where cellular uptake of the L-Cys QDs is almost twice as effective as that of the D-Cys QDs. This finding paves the way for the creation of novel approaches to control the biological properties and behavior of nanomaterials in living cells.

  14. Contributions of Atmospheric CO and Hydrogen Uptake to Microbial Dynamics on Recent Hawaiian Volcanic Deposits†

    PubMed Central

    King, Gary M.

    2003-01-01

    A series of sites were established on Hawaiian volcanic deposits ranging from about 18 to 300 years old. Three sites occurred in areas that supported tropical rain forests; the remaining sites were in areas that supported little or no plant growth. Sites >26 years old consumed atmospheric CO and hydrogen at rates ranging from about 0.2 to 5 mg of CO m−2 day−1 and 0.1 to 4 mg of H2 m−2 day−1, respectively. Respiration, measured as CO2 production, for a subset of the sites ranged from about 40 to >1,400 mg of CO2 m−2 day−1. CO and H2 accounted for about 13 to 25% of reducing equivalent flow for all but a forested site, where neither substrate appeared significant. Based on responses to chloroform fumigation, hydrogen utilization appeared largely due to microbial uptake. In contrast to results for CO and hydrogen, methane uptake occurred consistently only at the forest site. Increasing deposit age was generally accompanied by increasing concentrations of organic matter and microbial biomass, measured as phospholipid phosphate. Exoenzymatic activities (acid and alkaline phosphatases and α- and β-glucosidases) were positively correlated with deposit age in spite of considerable variability within sites. The diversity of substrates utilized in Biolog Ecoplate assays also increased with deposit age, possibly reflecting changes in microbial community complexity. PMID:12839783

  15. Exceptional ammonia uptake by a covalent organic framework

    NASA Astrophysics Data System (ADS)

    Doonan, Christian J.; Tranchemontagne, David J.; Glover, T. Grant; Hunt, Joseph R.; Yaghi, Omar M.

    2010-03-01

    Covalent organic frameworks (COFs) are porous crystalline materials composed of light elements linked by strong covalent bonds. A number of these materials contain a high density of Lewis acid boron sites that can strongly interact with Lewis basic guests, which makes them ideal for the storage of corrosive chemicals such as ammonia. We found that a member of the covalent organic framework family, COF-10, shows the highest uptake capacity (15 mol kg-1, 298 K, 1 bar) of any porous material, including microporous 13X zeolite (9 mol kg-1), Amberlyst 15 (11 mol kg-1) and mesoporous silica, MCM-41 (7.9 mol kg-1). Notably, ammonia can be removed from the pores of COF-10 by heating samples at 200 °C under vacuum. In addition, repeated adsorption of ammonia into COF-10 causes a shift in the interlayer packing, which reduces its apparent surface area to nitrogen. However, owing to the strong Lewis acid-base interactions, the total uptake capacity of ammonia and the structural integrity of the COF are maintained after several cycles of adsorption/desorption.

  16. Characterization of taurine binding, uptake, and release in the rat hypothalamus

    SciTech Connect

    Hanretta, A.T.

    1985-01-01

    The neurotransmitter criteria of specific receptors, inactivation, and release were experimentally examined for taurine in the hypothalamus. Specific membrane binding and synaptosomal uptake of taurine both displayed high affinity and low affinity systems. The neurotransmitter criterion of release was studied in superfused synaptosomes. Exposure of synaptosomes which had been preloaded with a concentration of (/sup 3/H)taurine in the high affinity uptake range (1.5 ..mu..M) to either 56 mM K/sup +/ or 100 ..mu..M veratridine evoked a Ca/sup 2 +/-independent release. Exposure of synaptosomes which had been preloaded with a concentration of (/sup 3/H)taurine in the low affinity uptake range (2 mM) to 56 mM K/sup +/ induced a Ca/sup 2 +/-independent release, whereas 100 /sup +/M veratridine did not, either in the presence or absence of Ca/sup 2 +/. Based on these results, as well as other observations, a model is proposed in which the high affinity uptake system is located on neuronal membranes and the low affinity uptake system is located on glial membranes. The mechanisms of binding, uptake, and release in relation to the cellular location of each are discussed. We conclude that the neurotransmitter criterion of activation by re-uptake is satisfied for taurine in the hypothalamus. However, the failure to demonstrate both a specific taurine receptor site and a Ca/sup 2 +/-dependent evoked release, necessitates that we conclude that taurine appears not to function as a hypothalamic neurotransmitter, at least not in the classical sense.

  17. Inhibition of Phosphate Uptake in Corn Roots by Aluminum-Fluoride Complexes1

    PubMed Central

    Façanha, Arnoldo Rocha; Okorokova-Façanha, Anna L.

    2002-01-01

    F forms stable complexes with Al at conditions found in the soil. Fluoroaluminate complexes (AlFx) have been widely described as effective analogs of inorganic phosphate (Pi) in Pi-binding sites of several proteins. In this work, we explored the possibility that the phytotoxicity of AlFx reflects their activity as Pi analogs. For this purpose, 32P-labeled phosphate uptake by excised roots and plasma membrane H+-ATPase activity were investigated in an Al-tolerant variety of maize (Zea mays L. var. dwarf hybrid), either treated or not with AlFx. In vitro, AlFx competitively inhibited the rate of root phosphate uptake as well as the H+-ATPase activity. Conversely, pretreatment of seedlings with AlFx in vivo promoted no effect on the H+-ATPase activity, whereas a biphasic effect on Pi uptake by roots was observed. Although the initial rate of phosphate uptake by roots was inhibited by AlFx pretreatment, this situation changed over the following minutes as the rate of uptake increased and a pronounced stimulation in subsequent 32Pi uptake was observed. This kinetic behavior suggests a reversible and competitive inhibition of the phosphate transporter by fluoroaluminates. The stimulation of root 32Pi uptake induced by AlFx pretreatment was tentatively interpreted as a phosphate starvation response. This report places AlF3 and AlF4− among Al-phytotoxic species and suggests a mechanism of action where the accumulation of Pi-mimicking fluoroaluminates in the soil may affect the phosphate absorption by plants. The biochemical, physiological, and environmental significance of these findings is discussed. PMID:12177489

  18. SITE RANK

    EPA Science Inventory

    Site rank is formulated for ranking the relative hazard of contamination sources and vulnerability of drinking water wells. Site rank can be used with a variety of groundwater flow and transport models.

  19. Extrapulmonary sites of radiogallium accumulation in sarcoidosis

    SciTech Connect

    Sulavik, S.B.; Palestro, C.J.; Spencer, R.P.; Swyer, A.J.; Goldsmith, S.J.; Tierstein, A.S. )

    1990-12-01

    In an effort to detect extrapulmonary sites of radiogallium accumulation in cases of sarcoidosis, 145 separate Ga-67 citrate studies of 114 patients with biopsy-proven sarcoidosis were examined. The most characteristic extrapulmonary radiogallium uptake pattern was the panda sign in 47 patients (41%). The most common site of prominent extrapulmonary radiogallium uptake was the lacrimal glands in 101 patients (88%). Second most common was activity in one or more superficial lymph node regions such as the cervical, axillary, femoral, or inguinal in 19 patients (17%). Other extrapulmonary sites included breast uptake in 6 out of 80 women (8%), prominent splenic and nasal uptake in 9 (8%) patients, periportal accumulation in 7 (6%), and cutaneous/subcutaneous activity in 4 (4%). Because many of these individuals were receiving corticosteroids, the natural (untreated) prevalence of extrapulmonary findings may be even higher. Although the sensitivity and specificity of extrapulmonary radiogallium accumulation has still to be determined, many of the sites may be accessible to biopsy both for diagnostic purposes and to follow the effects of medications. It is therefore suggested that whole-body imaging be performed when radiogallium is administered to patients with suspected or known sarcoidosis.

  20. Implications of abnormal right ventricular thallium uptake in acute myocardial infarction

    SciTech Connect

    Nestico, P.F.; Hakki, A.H.; Felsher, J.; Heo, J.; Iskandrian, A.S.

    1986-08-01

    The correlates of abnormal right ventricular (RV) thallium uptake were examined in 116 patients with documented acute myocardial infarction (AMI) who underwent predischarge thallium-201 scintigraphy at rest, radionuclide angiography and 24-hour ambulatory electrocardiography. The patients were separated into 2 groups: patients group 1 (n = 31) had increased RV thallium uptake and those in group 2 (n = 85) had no such uptake. The 2 groups were comparable in age, type and site of AMI, peak creatine kinase level, systolic blood pressure and heart rate. However, compared with group 2, group 1 had a lower mean left ventricular (LV) ejection fraction (33 +/- 15% vs 39 +/- 14%, p less than 0.05), higher prevalence of increased lung thallium uptake (45% vs 22%, p less than 0.02), more extensive LV perfusion defects (4.4 +/- 2.9 vs 3.0 +/- 3.0 segments, p less than 0.03) and more complex ventricular arrhythmias (55% vs 35%, p less than 0.05). At a mean follow-up of 6 months, 17 patients (8 in group 1 and 9 in group 2) died from cardiac causes. Actuarial life-table analysis showed that the survival rate was better in group 2 than in group 1 (Mantel-Cox statistics = 4.62, p = 0.03). Thus, patients with AMI and abnormal RV thallium uptake have worse LV function, more complex ventricular arrhythmias and worse prognosis.

  1. Uptake of corticosterone into isolated rat liver cells: possible involvement of Na+/K(+)-ATPase.

    PubMed

    Spindler, K D; Kanuma, K; Grossmann, D

    1991-06-01

    Isolated rat hepatocytes possess a saturable glucocorticoid uptake system with high affinity (Kd value = 2.8 +/- 0.7 x 10(-8) M; 318,000 +/- 80,000 binding sites per cell; 317 fmol/mg protein). The initial rates of uptake decrease by about 30-40% if the cells are incubated simultaneously with [3H]corticosterone and either SH-reagents (N-ethylmaleimide and p-chloromercuriphenylsulphonate, 1 mM), metabolic inhibitors (2,4-dinitrophenol, 1 mM; and antimycin, 0.1 mM) or the Na+/K(+)-ATPase-inhibitors, ouabain and quercetine. These Na+/K(+)-ATPase-blockers exert half-maximal inhibition at 3 x 10(-7) and 3 x 10(-6) M, respectively. A slight increase in K+ concentration and a corresponding decrease in Na+ in the medium leads to a significant reduction in the initial uptake rate. The uptake system from the rat hepatocytes shows a clear steroid specificity, being different from the intracellular receptor. Corticosterone and progesterone are the strongest competitors, cortisol, 5 alpha- and 5 beta-dihydrocorticosterone, 11-deoxycorticosterone, cortisone and testosterone have an intermediate effect and only weak competition is exerted by dexamethasone and by the mineralocorticoid, aldosterone. Estradiol and estrone sulphate as well as the synthetic glucocorticoid triamcinolone acetonide are unable to inhibit initial corticosterone uptake. PMID:1648377

  2. Influence of ornithine decarboxylase antizymes and antizyme inhibitors on agmatine uptake by mammalian cells.

    PubMed

    Ramos-Molina, Bruno; López-Contreras, Andrés J; Lambertos, Ana; Dardonville, Christophe; Cremades, Asunción; Peñafiel, Rafael

    2015-05-01

    Agmatine (4-aminobutylguanidine), a dicationic molecule at physiological pH, exerts relevant modulatory actions at many different molecular target sites in mammalian cells, having been suggested that the administration of this compound may have therapeutic interest. Several plasma membrane transporters have been implicated in agmatine uptake by mammalian cells. Here we report that in kidney-derived COS-7 cell line, at physiological agmatine levels, the general polyamine transporter participates in the plasma membrane translocation of agmatine, with an apparent Km of 44 ± 7 µM and Vmax of 17.3 ± 3.3 nmol h(-1) mg(-1) protein, but that at elevated concentrations, agmatine can be also taken up by other transport systems. In the first case, the physiological polyamines (putrescine, spermidine and spermine), several diguanidines and bis(2-aminoimidazolines) and the polyamine transport inhibitor AMXT-1501 markedly decreased agmatine uptake. In cells transfected with any of the three ornithine decarboxylase antizymes (AZ1, AZ2 and AZ3), agmatine uptake was dramatically reduced. On the contrary, transfection with antizyme inhibitors (AZIN1 and AZIN2) markedly increased the transport of agmatine. Furthermore, whereas putrescine uptake was significantly decreased in cells transfected with ornithine decarboxylase (ODC), the accumulation of agmatine was stimulated, suggesting a trans-activating effect of intracellular putrescine on agmatine uptake. All these results indicate that ODC and its regulatory proteins (antizymes and antizyme inhibitors) may influence agmatine homeostasis in mammalian tissues. PMID:25655388

  3. DOC:NO3- ratios and NO3- uptake in forested headwater streams

    NASA Astrophysics Data System (ADS)

    Rodríguez-Cardona, Bianca; Wymore, Adam S.; McDowell, William H.

    2016-01-01

    The underlying mechanisms driving the coupled interactions between inorganic nitrogen uptake and dissolved organic matter are not well understood, particularly in surface waters. To determine the relationship between dissolved organic carbon (DOC) quantity and nitrate (NO3-) uptake kinetics in streams, we performed a series of NO3- Tracer Additions for Spiraling Curve Characterization experiments in four streams within the Lamprey River Watershed, New Hampshire, across a range in background DOC concentrations (1-8 mg C/L). Experiments were performed throughout the 2013 and 2014 growing seasons. Across streams and experimental dates, ambient uptake velocity (Vf) correlated positively with increasing DOC concentrations and DOC:NO3- ratios but was only weakly negatively associated with NO3- concentrations. Ambient NO3- Vf was unrelated to pH, light, temperature, dissolved oxygen, and Specific Ultraviolet Absorbance at 254 nm. Although there were general tendencies across the entire Lamprey River Watershed, individual sites behaved differently in their uptake kinetics. NO3- uptake dynamics in the Lamprey River Watershed are most strongly influenced by DOC concentrations rather than NO3- concentrations or physicochemical parameters, which have been identified as regional- to continental-scale drivers in previous research. Understanding the fundamental relationships between dissolved organic matter and inorganic nutrients will be important as global and climatic changes influence the delivery and production of DOC and NO3- in aquatic ecosystems.

  4. The gut wall provides an effective barrier against nanoparticle uptake

    PubMed Central

    Sinnecker, Heike; Krause, Thorsten; Koelling, Sabine; Lautenschläger, Ingmar

    2014-01-01

    Summary Background: The omnipresence of nanoparticles (NPs) in numerous goods has led to a constant risk of exposure and inadvertent uptake for humans. This situation calls for thorough investigation of the consequences of NP intake. As the vast mucosa of the human gastrointestinal tract represents an attractive site of entry, we wanted to take a look on the fate that ingested NPs suffer in the gut. As a model to investigate NP uptake we used the isolated perfused rat small intestine. Differently sized fluorescent latex particles were used as exemplary anthropogenic NPs. Results: The particles were administered as bolus into the isolated intestine, and samples from the luminal, vascular and lymphatic compartments were collected over time. NP amounts in the different fluids were determined by fluorescence measurements. No particles could be detected in the vascular and lymphatic system. By contrast a major amount of NPs was found in luminal samples. Yet, a substantial share of particles could not be recovered in the fluid fractions, indicating a sink function of the intestinal tissue for NPs. A histological examination of the gut revealed that virtually no particles adhered to the epithelium or resided in the tissue, the bulk of particles seemed to be trapped in the mucus lining the gut tube. When this mucus was dissolved and removed from the gut almost the entire amount of particles missing could be recovered: over 95% of the given NPs were present in the two fractions, the luminal samples and the dissolved mucus. To foster NP uptake via an extended interaction time with the epithelium, the intestinal peristalsis was decelerated and the duration of the experiment was prolonged. Even under those conditions, no particle fluorescence was detected in the vascular and lymphatic samples. Conclusion: We could show that after intestinal exposure with a large dose of NPs the vast majority of NPs did obviously not come into contact with the epithelium but was either directly

  5. Iron, nitrate uptake by phytoplankton, and mermaids

    NASA Astrophysics Data System (ADS)

    Banse, Karl

    1991-11-01

    The critique by Martin et al. (this issue) of my recalculation of rates of nitrate uptake, and hence of algal division, from the Gulf of Alaska is shown to be incorrect. Neither can iron deficiency, if any, be shown to be connected with the demise of mermen and mermaids, although for different reasons.

  6. Water uptake in stimulated cat skeletal muscle.

    PubMed

    Watson, P D; Garner, R P; Ward, D S

    1993-04-01

    Isolated vasodilated cat hindlimb skeletal muscles were perfused at constant flow and stimulated at 4 Hz for 2-4 min in three studies. Water uptake rates were measured gravimetrically or calculated from venous protein concentration changes. Venous plasma sodium, potassium, chloride, and osmolality were also measured. Maximum water uptake rates averaged 1.8 +/- 0.2 (SE) ml.min-1 x 100 g-1, reaching twice that in some experiments. Water uptake continued after stimulation had ceased. Constant-flow perfusion maintained a constant capillary pressure that was corroborated by measurements of arterial and venous perfusate pressures. Water uptake rate was not influenced by hematocrit but was highly correlated with plasma flow rate. The evidence strongly suggests that small-molecule osmotic pressure was the primary pressure causing the transcapillary water flux. Venous plasma sodium and chloride concentrations increased almost as much as protein (108 and 87% of the protein increase, respectively), as would be expected when water fluxes are driven by small-molecule osmotic pressure. Peak potassium efflux averaged 36 +/- 3 mu eq.min-1 x 100 g-1, but potassium did not contribute significantly to the osmotic gradient. PMID:8476122

  7. Statins impair glucose uptake in human cells

    PubMed Central

    Nowis, Dominika; Malenda, Agata; Furs, Karolina; Oleszczak, Bozenna; Sadowski, Radoslaw; Chlebowska, Justyna; Firczuk, Malgorzata; Bujnicki, Janusz M; Staruch, Adam D; Zagozdzon, Radoslaw; Glodkowska-Mrowka, Eliza; Szablewski, Leszek; Golab, Jakub

    2014-01-01

    Objective Considering the increasing number of clinical observations indicating hyperglycemic effects of statins, this study was designed to measure the influence of statins on the uptake of glucose analogs by human cells derived from liver, adipose tissue, and skeletal muscle. Design Flow cytometry and scintillation counting were used to measure the uptake of fluorescently labeled or tritiated glucose analogs by differentiated visceral preadipocytes, skeletal muscle cells, skeletal muscle myoblasts, and contact-inhibited human hepatocellular carcinoma cells. A bioinformatics approach was used to predict the structure of human glucose transporter 1 (GLUT1) and to identify the presence of putative cholesterol-binding (cholesterol recognition/interaction amino acid consensus (CRAC)) motifs within this transporter. Mutagenesis of CRAC motifs in SLC2A1 gene and limited proteolysis of membrane GLUT1 were used to determine the molecular effects of statins. Results Statins significantly inhibit the uptake of glucose analogs in all cell types. Similar effects are induced by methyl-β-cyclodextrin, which removes membrane cholesterol. Statin effects can be rescued by addition of mevalonic acid, or supplementation with exogenous cholesterol. Limited proteolysis of GLUT1 and mutagenesis of CRAC motifs revealed that statins induce conformational changes in GLUTs. Conclusions Statins impair glucose uptake by cells involved in regulation of glucose homeostasis by inducing cholesterol-dependent conformational changes in GLUTs. This molecular mechanism might explain hyperglycemic effects of statins observed in clinical trials. PMID:25452863

  8. PLANT UPTAKE OF SLUDGE-BORNE PCBS

    EPA Science Inventory

    Plant uptake of sludge-borne polychlorinated biphenyls (PCBs) (similar to Aroclor 1248) was evaluated in a greenhouse study with two food-chain crops and a grass species. olychlorinated biphenyl loading to two soils was varied in one experiment by adding different rates of a muni...

  9. Routes and mechanisms of extracellular vesicle uptake

    PubMed Central

    Mulcahy, Laura Ann; Pink, Ryan Charles; Carter, David Raul Francisco

    2014-01-01

    Extracellular vesicles (EVs) are small vesicles released by donor cells that can be taken up by recipient cells. Despite their discovery decades ago, it has only recently become apparent that EVs play an important role in cell-to-cell communication. EVs can carry a range of nucleic acids and proteins which can have a significant impact on the phenotype of the recipient. For this phenotypic effect to occur, EVs need to fuse with target cell membranes, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest because they are deregulated in diseases such as cancer and they could be harnessed to deliver drugs to target cells. It is therefore important to understand the molecular mechanisms by which EVs are taken up into cells. This comprehensive review summarizes current knowledge of EV uptake mechanisms. Cells appear to take up EVs by a variety of endocytic pathways, including clathrin-dependent endocytosis, and clathrin-independent pathways such as caveolin-mediated uptake, macropinocytosis, phagocytosis, and lipid raft–mediated internalization. Indeed, it seems likely that a heterogeneous population of EVs may gain entry into a cell via more than one route. The uptake mechanism used by a given EV may depend on proteins and glycoproteins found on the surface of both the vesicle and the target cell. Further research is needed to understand the precise rules that underpin EV entry into cells. PMID:25143819

  10. INFLUENCE OF GROWTH REGULATORS ON PESTICIDE UPTAKE

    EPA Science Inventory

    The purpose of this study was to significantly reduce the amounts of herbicides necessary to control certain noxious weeds. In laboratory and field studies herbicides were applied with certain plant hormones to accelerate their uptake and translocation in plants. Treatment of red...

  11. New concepts for dynamic plant uptake models.

    PubMed

    Rein, A; Legind, C N; Trapp, S

    2011-03-01

    Models for the prediction of chemical uptake into plants are widely applied tools for human and wildlife exposure assessment, pesticide design and for environmental biotechnology such as phytoremediation. Steady-state considerations are often applied, because they are simple and have a small data need. However, often the emission pattern is non-steady. Examples are pesticide spraying, or the application of manure and sewage sludge on agricultural fields. In these scenarios, steady-state solutions are not valid, and dynamic simulation is required. We compared different approaches for dynamic modelling of plant uptake in order to identify relevant processes and timescales of processes in the soil-plant-air system. Based on the outcome, a new model concept for plant uptake models was developed, approximating logistic growth and coupling transpiration to growing plant mass. The underlying system of differential equations was solved analytically for the inhomogenous case, i.e. for constant input. By superposition of the results of n periods, changes in emission and input data between periods are considered. This combination allows to mimic most input functions that are relevant in practice. The model was set up, parameterized and tested for uptake into growing crops. The outcome was compared with a numerical solution, to verify the mathematical structure. PMID:21391147

  12. Improving PMTCT Uptake in Rural South Africa

    PubMed Central

    Weiss, S. M.; Peltzer, K.; Villar-Loubet, O.; Shikwane, M. E.; Cook, R.; Jones, D. L.

    2016-01-01

    Introduction Despite the widespread availability of prevention of mother-to-child transmission (PMTCT) programs, many women in sub-Saharan Africa do not participate in PMTCT. This pilot study aimed to utilize partner participation in an intervention to support PMTCT uptake. Methods Couples (n = 239) were randomized to receive either a comprehensive couples-based PMTCT intervention or the standard of care. Results Compared to the standard of care, participants receiving the intervention increased HIV- and PMTCT-related knowledge (F1,474 = 13.94, p = .004) and uptake of PMTCT, as defined by infant medication dosing (74% vs. 46%, χ2 = 4.69, p = .03). Discussion Results indicate that increasing male attendance at antenatal clinic visits may be “necessary but not sufficient” to increase PMTCT uptake. Increasing HIV knowledge of both partners and encouraging active male participation in the PMTCT process through psychoeducational interventions may be a strategy to increase the uptake of PMTCT in South Africa. PMID:23778240

  13. NUTRIENT-UPTAKE MODEL IN MARSH ECOSYSTEMS

    EPA Science Inventory

    Mechanistic models of nutrient dynamics in natural wetlands were developed and applied in a study of Kissimmee River (Florida) flood-plain marshes. The models describe hydrodynamics and transport diffusion in wetland basins and the ecological processes of nutrient uptake, convers...

  14. Bicarbonate uptake by Southern Ocean phytoplankton

    NASA Astrophysics Data System (ADS)

    Cassar, Nicolas; Laws, Edward A.; Bidigare, Robert R.; Popp, Brian N.

    2004-06-01

    Marine phytoplankton have the potential to significantly buffer future increases in atmospheric carbon dioxide levels. However, in order for CO2 fertilization to have an effect on carbon sequestration to the deep ocean, the increase in dissolved CO2 must stimulate primary productivity; that is, marine phototrophs must be CO2 limited [, 1993]. Estimation of the extent of bicarbonate (HCO3-) uptake in the oceans is therefore required to determine whether the anthropogenic carbon sources will enhance carbon flux to the deep ocean. Using short-term 14CO2-disequilibrium experiments during the Southern Ocean Iron Experiment (SOFeX), we show that HCO3- uptake by Southern Ocean phytoplankton is significant. Since the majority of dissolved inorganic carbon (DIC) in the ocean is in the form of bicarbonate, the biological pump may therefore be insensitive to anthropogenic CO2. Approximately half of the DIC uptake observed was attributable to direct HCO3- uptake, the other half being direct CO2 uptake mediated either by passive diffusion or active uptake mechanisms. The increase in growth rates and decrease in CO2 concentration associated with the iron fertilization did not trigger any noticeable changes in the mode of DIC acquisition, indicating that under most environmental conditions the carbon concentrating mechanism (CCM) is constitutive. A low-CO2 treatment induced an increase in uptake of CO2, which we attributed to increased extracellular carbonic anhydrase activity, at the expense of direct HCO3- transport across the plasmalemma. Isotopic disequilibrium experimental results are consistent with Southern Ocean carbon stable isotope fractionation data from this and other studies. Although iron fertilization has been shown to significantly enhance phytoplankton growth and may potentially increase carbon flux to the deep ocean, an important source of the inorganic carbon taken up by phytoplankton in this study was HCO3-, whose concentration is negligibly affected by the

  15. Uptake rates of thorium progeny in a semiarid environment.

    PubMed

    McClellan, Yvonne; August, Robert; Gosz, James; Gann, Steve; Parmenter, Robert; Nelson, Martin; Harper, Mark

    2003-01-01

    The release rates and transformation processes that influence the mobility, biological uptake, and transfer of radionuclides are essential to the assessment of the health effects in the food chain and ecosystem. This study examined concentrations of 222Th in both soil and vegetation at a closed military training site, Kirtland Air Force Base (KAFB), New Mexico. Brazilian sludge was intentionally introduced into the topsoil in the early 1960s to simulate nuclear weapon accidents. Soil (60) and vegetation (120) samples were collected from 1996 to 2000 and analyzed for radionuclides and progeny. High-resolution gamma-ray spectroscopy was used to determine radionuclide activities. The results indicate that the thorium progeny were the predominant contaminant in soil and vegetation. Concentration ratios (CRs) were calculated based on actinium levels. PMID:14535318

  16. Increasing uptake of bowel cancer screening

    PubMed Central

    Graham, Sarah

    2014-01-01

    Uptake of bowel cancer screening uptake at our practice is 32.72%, which is below the national target of 60%, but our cancer prevalence and death rate is higher than our CCG statistical mean. We examined reasons for non-response to bowel cancer screening in our patients and explored ways to promote engagement. From August 2013 to February 2014 we used three interventions in two patient groups: those turning 60 and eligible for screening (rising 60's) and non-responders to screening. Interventions used were; letter encouragement for rising 60's, staff education to increase opportunistic promotion of screening and calling non- responders to identify reasons for non-participation and encourage participation. Calls were made by either a Doctor or a Health Care Assistant (HCA); ethnicity, language spoken, caller and call outcome was recorded. Rising 60's (n=26) had an uptake of 46%, increased from 32.72%. From the non-responders (n = 73) we were unable to contact 38%, 46% was due to an incorrect or no phone number. Of those contacted main reasons for non-participation were not receiving a screening kit (n=19) and not wanting to be screened (n=14). Following calls 66% of non-responders agreed to screening. From this 66% half (50%) completed screening with a negative result. 15 non-responders refused screening following our calls, the main reason given was not wanting to know if they had cancer (n =14). Calls from doctor and HCA had similar rates of screening uptake (39% and 33% respectively). Difficulty contacting patients was an unexpected barrier to screening and will be addressed. Actively encouraging screening appears beneficial with similar responses to Doctor and HCA. There appears to be a place for increased education regarding screening and early detection of malignancy amongst patients. Overall our interventions improved screening uptake at the practice and will be continued in future.

  17. Species turnover (β-diversity) in ectomycorrhizal fungi linked to NH4+ uptake capacity.

    PubMed

    Kranabetter, J M; Hawkins, B J; Jones, M D; Robbins, S; Dyer, T; Li, T

    2015-12-01

    Ectomycorrhizal (EcM) fungal communities may be shaped by both deterministic and stochastic processes, potentially influencing ecosystem development and function. We evaluated community assembly processes for EcM fungi of Pseudotsuga menziesii among 12 sites up to 400 km apart in southwest British Columbia (Canada) by investigating species turnover (β-diversity) in relation to soil nitrogen (N) availability and physical distance. We then examined functional traits for an N-related niche by quantifying net fluxes of NH4+, NO3- and protons on excised root tips from three contrasting sites using a microelectrode ion flux measurement system. EcM fungal communities were well aligned with soil N availability and pH, with no effect of site proximity (distance-decay curve) on species assemblages. Species turnover was significant (β(1/2) = 1.48) along soil N gradients, with many more Tomentella species on high N than low N soils, in contrast to Cortinarius species. Ammonium uptake was greatest in the spring on the medium and rich sites and averaged over 190 nmol/m(2)/s for Tomentella species. The lowest uptake rates of NH4+ were by nonmycorrhizal roots of axenically grown seedlings (10 nmol/m(2)/s), followed by Cortinarius species (60 nmol/m(2)/s). EcM roots from all sites displayed only marginal uptake of nitrate (8.3 nmol/m(2)/s). These results suggest NH4+ uptake capacity is an important functional trait influencing the assembly of EcM fungal communities. The diversity of EcM fungal species across the region arguably provides critical belowground adaptations to organic and inorganic N supply that are integral to temperate rainforest ecology. PMID:26507980

  18. Carbonyl sulfide exchange in soils for better estimates of ecosystem carbon uptake

    DOE PAGESBeta

    Whelan, Mary E.; Hilton, Timothy W.; Berry, Joseph A.; Berkelhammer, Max; Desai, Ankur R.; Campbell, J. Elliott

    2016-03-21

    Carbonyl sulfide (COS) measurements are one of the emerging tools to better quantify gross primary production (GPP), the largest flux in the global carbon cycle. COS is a gas with a similar structure to CO2; COS uptake is thought to be a proxy for GPP. However, soils are a potential source or sink of COS. This study presents a framework for understanding soil–COS interactions. Excluding wetlands, most of the few observations of isolated soils that have been made show small uptake of atmospheric COS. Recently, a series of studies at an agricultural site in the central United States found soilmore » COS production under hot conditions an order of magnitude greater than fluxes at other sites. To investigate the extent of this phenomenon, soils were collected from five new sites and incubated in a variety of soil moisture and temperature states. We found that soils from a desert, an oak savannah, a deciduous forest, and a rainforest exhibited small COS fluxes, behavior resembling previous studies. However, soil from an agricultural site in Illinois, >800 km away from the initial central US study site, demonstrated comparably large soil fluxes under similar conditions. These new data suggest that, for the most part, soil COS interaction is negligible compared to plant uptake of COS. We present a model that anticipates the large agricultural soil fluxes so that they may be taken into account. Furthermore, while COS air-monitoring data are consistent with the dominance of plant uptake, improved interpretation of these data should incorporate the soil flux parameterizations suggested here.« less

  19. Carbonyl sulfide exchange in soils for better estimates of ecosystem carbon uptake

    SciTech Connect

    Whelan, Mary E.; Hilton, Timothy W.; Berry, Joseph A.; Berkelhammer, Max; Desai, Ankur R.; Campbell, J. Elliott

    2016-01-01

    Carbonyl sulfide (COS) measurements are one of the emerging tools to better quantify gross primary production (GPP), the largest flux in the global carbon cycle. COS is a gas with a similar structure to CO2; COS uptake is thought to be a proxy for GPP. However, soils are a potential source or sink of COS. This study presents a framework for understanding soil–COS interactions. Excluding wetlands, most of the few observations of isolated soils that have been made show small uptake of atmospheric COS. Recently, a series of studies at an agricultural site in the central United States found soil COS production under hot conditions an order of magnitude greater than fluxes at other sites. To investigate the extent of this phenomenon, soils were collected from five new sites and incubated in a variety of soil moisture and temperature states. We found that soils from a desert, an oak savannah, a deciduous forest, and a rainforest exhibited small COS fluxes, behavior resembling previous studies. However, soil from an agricultural site in Illinois,  > 800 km away from the initial central US study site, demonstrated comparably large soil fluxes under similar conditions. These new data suggest that, for the most part, soil COS interaction is negligible compared to plant uptake of COS. We present a model that anticipates the large agricultural soil fluxes so that they may be taken into account. While COS air-monitoring data are consistent with the dominance of plant uptake, improved interpretation of these data should incorporate the soil flux parameterizations suggested here.

  20. Carbonyl sulfide exchange in soils for better estimates of ecosystem carbon uptake

    NASA Astrophysics Data System (ADS)

    Whelan, M. E.; Hilton, T. W.; Berry, J. A.; Berkelhammer, M.; Desai, A. R.; Campbell, J. E.

    2015-08-01

    Carbonyl sulfide (COS) measurements are one of the emerging tools to better quantify gross primary production (GPP), the largest flux in the global carbon cycle. COS is a gas with a similar structure to CO2; COS uptake is thought to be a proxy for GPP. However, soils are a potential source or sink of COS. This study presents a framework for understanding soil-COS interactions. Excluding wetlands, most of the few observations of isolated soils that have been made show small uptake of atmospheric COS. Recently, a series of studies at an agricultural site in the central United States found soil COS production under hot conditions an order of magnitude greater than fluxes at other sites. To investigate the extent of this phenomenon, soils were collected from 5 new sites and incubated in a variety of soil moisture and temperature states. We found that soils from a desert, an oak savannah, a deciduous forest, and a rainforest exhibited small COS fluxes, behavior resembling previous studies. However, soil from an agricultural site in Illinois, > 800 km away from the initial central US study site, demonstrated comparably large soil fluxes under similar conditions. These new data suggest that, for the most part, soil COS interaction is negligible compared to plant uptake of COS. We present a model that anticipates the large agricultural soil fluxes so that they may be taken into account. While COS air-monitoring data are consistent with the dominance of plant uptake, improved interpretation of these data should incorporate the soil flux parameterizations suggested here.

  1. Carbonyl sulfide exchange in soils for better estimates of ecosystem carbon uptake

    NASA Astrophysics Data System (ADS)

    Whelan, Mary E.; Hilton, Timothy W.; Berry, Joseph A.; Berkelhammer, Max; Desai, Ankur R.; Campbell, J. Elliott

    2016-03-01

    Carbonyl sulfide (COS) measurements are one of the emerging tools to better quantify gross primary production (GPP), the largest flux in the global carbon cycle. COS is a gas with a similar structure to CO2; COS uptake is thought to be a proxy for GPP. However, soils are a potential source or sink of COS. This study presents a framework for understanding soil-COS interactions. Excluding wetlands, most of the few observations of isolated soils that have been made show small uptake of atmospheric COS. Recently, a series of studies at an agricultural site in the central United States found soil COS production under hot conditions an order of magnitude greater than fluxes at other sites. To investigate the extent of this phenomenon, soils were collected from five new sites and incubated in a variety of soil moisture and temperature states. We found that soils from a desert, an oak savannah, a deciduous forest, and a rainforest exhibited small COS fluxes, behavior resembling previous studies. However, soil from an agricultural site in Illinois, > 800 km away from the initial central US study site, demonstrated comparably large soil fluxes under similar conditions. These new data suggest that, for the most part, soil COS interaction is negligible compared to plant uptake of COS. We present a model that anticipates the large agricultural soil fluxes so that they may be taken into account. While COS air-monitoring data are consistent with the dominance of plant uptake, improved interpretation of these data should incorporate the soil flux parameterizations suggested here.

  2. Investigating phosphorus uptake in anoxic and sulfidic surface sediments with 33P radiotracer experiments

    NASA Astrophysics Data System (ADS)

    Dijkstra, Nikki; Kraal, Peter; Gonzalez, Santiago; Slomp, Caroline

    2016-04-01

    Phosphorus (P) is a key nutrient for marine organisms. Enhanced P availability in the water column can fuel algal blooms and the development of bottom water anoxia. Recently, it was suggested that micro-organisms in sediments overlain by anoxic and sulfidic bottom waters might take up dissolved P and form Fe(II)-P minerals, thereby enhancing P removal. In this study, we investigated the uptake of P in surface sediments with 33P radiotracer experiments. The sediments were recovered from the anoxic and sulfidic deep basin of the Black Sea and, for comparison, from the adjacent oxic shelf. Results suggest a very fast sedimentary uptake of 33P at all sites but in particular for sediments from the oxic shelf. At all sites, most 33P was sequestered in the citrate-dithionite-bicarbonate-(CDB)-extractable sediment P fraction. No significant differences with abiotic controls were observed, implying that micro-organisms were not directly involved in the P uptake. Whereas 33P uptake by the oxic shelf sediment was likely controlled by sorption of 33P to iron(Fe)-(oxyhydr)oxides, the nature of the CDB-extractable P fraction in the deep basin sediments remains unclear. We discuss whether authigenic formation of Fe(II)-P minerals or fast adsorption of P to calcites may explain our findings.

  3. Imipramine treatment differentially affects platelet /sup 3/H-imipramine binding and serotonin uptake in depressed patients

    SciTech Connect

    Suranyi-Cadotte, B.E.; Quirion, R.; Nair, N.P.V.; Lafaille, F.; Schwartz, G.

    1985-02-25

    Uptake of serotonin and /sup 3/H-imipramine binding in platelets of depressed patients were investigated simultaneously with changes in clinical state. Both V/sub max/ for serotonin uptake and B/sub max/ for /sup 3/H-imipramine binding were significantly lower in unmedicated depressed patients with respect to normal subjects. Successful treatment with imipramine led to a significant increase in B/sub max/ for /sup 3/H-imipramine binding, without significant change in V/sub max/ for serotonin uptake. B/sub max/ values increased to the normal range following complete, rather than partial clinical improvement. These data indicate that successful antidepressant treatment may increase the density of /sup 3/H-imipramine binding sites on platelets by a process which is independent of the uptake of serotonin. 29 references, 1 table.

  4. Effects of ammonium and nitrate on nutrient uptake and activity of nitrogen assimilating enzymes in western hemlock

    SciTech Connect

    Knoepp, J.D.; Turner, D.P.; Tingey, D.T.

    1993-01-01

    Western hemlock seedlings were grown in nutrient solutions with ammonium, nitrate or ammonium plus nitrate as nitrogen sources. The objectives were to examine (1) possible selectivity for ammonium or nitrate as an N source, (2) the maintenance of charge balance during ammonium and nitrate uptake, and (3) the activity of the nitrogen assimilating enzymes, nitrate reductase, glutamine synthetase, and glutamine dehydrogenase, in relation to the uptake of different nitrogen sources. The uptake studies revealed that western hemlock takes up ammonium faster than nitrate and that ammonium partially inhibits nitrate uptake. Nitrate reductase activity varied with nitrate availability in root tissue, but showed no response in needles, indicating that most nitrate is reduced in the roots. Results indicate that western hemlock may be adapted to sites where NH(4+) is the predominate N source.

  5. Comparing Measures of Fine Root Uptake by Mature Trees: Applications for Determining the Potential Impacts of Climate Change-Induced Soil Freezing on Nutrient Uptake by Sugar Maple and Red Spruce

    NASA Astrophysics Data System (ADS)

    Socci, A. M.; Templer, P. H.

    2008-12-01

    and the peak growing seasons. Rates of nutrient uptake by intact roots were significantly greater than rates of uptake by excised roots for both sugar maple and red spruce. Despite this difference, the patterns of NH4+ uptake compared to NO3- uptake were consistent across both methods. These results suggest that both means of measuring root nutrient uptake may be sufficient for comparing relative treatment effects across sites. However, the observed variation in magnitude suggests that caution must be taken in interpreting actual rates of uptake from either method.

  6. Characterization of (+/-)-methadone uptake by rat lung.

    PubMed Central

    Chi, C H; Dixit, B N

    1977-01-01

    1. By use of a sensitive and specific fluorescence assay procedure it was shown that after subcutaneous administration to rats, (+/-)-methadone was concentrated in the lung. Lung to serum ratios ranging from 25 to 60 were obtained indicating that the rat lung tissue was capable of extracting (+/-)-methadone against a concentration gradient. 2. This phenomenon was investigated in vitro with rat lung slices incubated in Krebs-Ringer phosphate buffer (pH 7.4). The uptake was expressed in terms of tissue to medium concentration ratios (T/M ratio). 3. The principal observations were: (i) Studies on the time-course of the uptake showed that the T/M ratios of (+/-)-methadone increased rapidly during the first 60 min of incubation and then more slowly, with a plateau occurring at 180 min; (ii) The T/M ratio of (+/-)-methadone progressively increased from 9.5 to 17 as the pH of the incubation medium was varied from 6.2 to 7.5; (iii) When the concentration of (+/-)-methadone in the incubation medium was varied from 0.005 to 0.5 mM, the T/M ratio decreased rapidly suggesting self-saturation of the transport process. Beyond the medium concentration of 0.5 mM, the T/M ratio declined very slowly. 4. These results suggested that at low concentrations, (+/-)-methadone was transported predominantly by a self-saturable process while at higher concentrations it was transported by a process of simple diffusion. 5. At low concentrations (0.01 mM) the uptake of (+)-methadone was higher than that of (-)-isomer indicating stereo-specificity of the uptake process. The uptake of (+/-)-methadone at low concentration (0.01 mM) was significantly inhibited by low temperature, lack of O2, lack of glucose, lack of Na+ in the incubation medium, and by exposure of the tissue to high temperature (approximately 100 degrees C). The uptake was also inhibited by relatively high concentration of iodoacetate (1.0 mM) and of naloxone (1.0 mM). 6. Kinetic analysis of data showed that the diffusion constant

  7. OXYGEN UPTAKE AND NUTRIENT REGENERATION IN THE PECONIC ESTUARY

    EPA Science Inventory

    EXECUTIVE SUMMARY: OXYGEN UPTAKE AND NUTRIENT REGENERATION IN THE PECONIC ESTUARY Rates of oxygen consumption and nutrient regeneration were measured annually throughout the Peconic Estuarine System. Sediment and water column oxygen uptake were measured to determine the potential...

  8. Uptake of myocardial imaging agents by rejected hearts

    SciTech Connect

    Bergsland, J.; Carr, E.A.; Carroll, M.; Wright, J.W.; Feldman, M.J.; Massucci, J.; Bhayana, J.N.; Gona, J.M.

    1985-09-01

    Technetium 99 m pyrophosphate, Gallium 67 and Thallium 201 uptakes were measured in heterotopically transplanted rat hearts. Five days after transplantation, Technetium 99 m pyrophosphate, and Gallium 67 uptakes were significantly higher in allogeneic grafts than in syngeneic grafts. At an early stage of rejection (three days after transplantation), only Technetium 99 m pyrophosphate uptake in the left ventricle of allogeneic grafts showed a significant difference (p less than 0.04). At five days, Thallium 201 uptake was significantly lower in allo- than syngeneic grafts. There was a positive correlation between radionuclide uptake and histologic degree of rejection for Technetium 99 m pyrophosphate and Gallium 67 while Thallium 201 uptake correlated negatively. Analysis of variance revealed that hearts with no or minimal rejection had statistically different uptakes than hearts with mild to moderate rejection. These results suggest that uptake of imaging agents might be useful in the diagnosis of rejection of the transplanted heart.

  9. Influence of the physicochemical characteristics of pollutants on their uptake in moss

    NASA Astrophysics Data System (ADS)

    Varela, Z.; Fernández, J. A.; Real, C.; Carballeira, A.; Aboal, J. R.

    2015-02-01

    Bryophytes are commonly used as biomonitors to estimate the atmospheric deposition of heavy metals and metalloids. However, the tissue concentrations of these elements in moss do not always accurately reflect atmospheric levels. The aim of the present study was to investigate whether element uptake in moss is affected by the physicochemical characteristics of the elements. Factor analysis was used to identify any patterns of covariance in the accumulation of elements in samples of the moss Pseudoscleropodium purum collected from the surroundings of different factories and from control sites. The variation in the concentrations of elements was similar in moss from both types of sites and was related to the binding properties of the elements. This suggests that the physicochemical characteristics of the elements determine the uptake of metals and metalloids from the atmosphere. Therefore, in studies that use multiple correlations among elements as indicators of a common origin of contaminants, erroneous conclusions may be reached by overlooking the adsorption properties of the moss.

  10. An exposure system for measuring nasal and lung uptake of vapors in rats

    SciTech Connect

    Dahl, A.R.; Brookins, L.K.; Gerde, P.

    1995-12-01

    Inhaled gases and vapors often produce biological damage in the nasal cavity and lower respiratory tract. The specific site within the respirator tract at which a gas or vapor is absorbed strongly influences the tissues at risk to potential toxic effects; to predict or to explain tissue or cell specific toxicity of inhaled gases or vapors, the sites at which they are absorbed must be known. The purpose of the work reported here was to develop a system for determining nose and lung absorption of vapors in rats, an animal commonly used in inhalation toxicity studies. In summary, the exposure system described allows us to measure in the rate: (1) nasal absorption and desorption of vapors; (2) net lung uptake of vapors; and (3) the effects of changed breathing parameters on vapor uptake.

  11. Factors influencing the uptake of orthodontic treatment.

    PubMed

    O'Brien, K; McComb, J L; Fox, N; Wright, J

    1996-11-01

    The aim of this investigation was to evaluate the factors that influenced the uptake of orthodontic treatment for patients who were referred for orthodontic treatment to two types of orthodontic treatment provider; a fee per item and hospital service. The following data were collected: (i) basic demographic data; (ii) the need for orthodontic treatment as measured by IOTN; and (iii) the outcome of the consultation. The data analysis with logistic regression revealed that the following variables had a predictive effect on the uptake of treatment: (i) the need for orthodontic treatment; and (ii) the patient's gender. Most of the patients that were referred and accepted for treatment had a definite need for orthodontic treatment. PMID:8985570

  12. Hydrogen Uptake of DPB Getter Pellets

    SciTech Connect

    Dinh, L N; Schildbach, M A; Herberg, J L; Saab, A P; Weigle, J; Chinn, S C; Maxwell, R S; McLean II, W

    2008-05-30

    The physical and chemical properties of 1,4-diphenylbutadiyne (DPB) blended with carbon-supported Pd (DPB-Pd/C) in the form of pellets during hydrogenation were investigated. A thermogravimetric analyzer (TGA) was employed to measure the kinetics of the hydrogen uptake by the DPB getter pellets. The kinetics obtained were then used to develop a semi-empirical model, based on gas diffusion into solids, to predict the performance of the getter pellets under various conditions. The accuracy of the prediction model was established by comparing the prediction models with independent experimental data on hydrogen pressure buildup in sealed systems containing DPB getter pellets and subjected to known rates of hydrogen input. The volatility of the hydrogenated DPB products and its effects on the hydrogen uptake kinetics were also analyzed.

  13. 21 CFR 886.1670 - Ophthalmic isotope uptake probe.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ophthalmic isotope uptake probe. 886.1670 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1670 Ophthalmic isotope uptake probe. (a) Identification. An ophthalmic isotope uptake probe is an AC-powered device intended to...

  14. 21 CFR 886.1670 - Ophthalmic isotope uptake probe.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ophthalmic isotope uptake probe. 886.1670 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1670 Ophthalmic isotope uptake probe. (a) Identification. An ophthalmic isotope uptake probe is an AC-powered device intended to...

  15. 21 CFR 886.1670 - Ophthalmic isotope uptake probe.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ophthalmic isotope uptake probe. 886.1670 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1670 Ophthalmic isotope uptake probe. (a) Identification. An ophthalmic isotope uptake probe is an AC-powered device intended to...

  16. 21 CFR 886.1670 - Ophthalmic isotope uptake probe.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ophthalmic isotope uptake probe. 886.1670 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1670 Ophthalmic isotope uptake probe. (a) Identification. An ophthalmic isotope uptake probe is an AC-powered device intended to...

  17. 21 CFR 886.1670 - Ophthalmic isotope uptake probe.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ophthalmic isotope uptake probe. 886.1670 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1670 Ophthalmic isotope uptake probe. (a) Identification. An ophthalmic isotope uptake probe is an AC-powered device intended to...

  18. Capturing Individual Uptake: Toward a Disruptive Research Methodology

    ERIC Educational Resources Information Center

    Bastian, Heather

    2015-01-01

    This article presents and illustrates a qualitative research methodology for studies of uptake. It does so by articulating a theoretical framework for qualitative investigations of uptake and detailing a research study designed to invoke and capture students' uptakes in a first-year writing classroom. The research design sought to make uptake…

  19. 21 CFR 892.1320 - Nuclear uptake probe.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nuclear uptake probe. 892.1320 Section 892.1320...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1320 Nuclear uptake probe. (a) Identification. A nuclear uptake probe is a device intended to measure the amount of radionuclide taken up by...

  20. 21 CFR 892.1320 - Nuclear uptake probe.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nuclear uptake probe. 892.1320 Section 892.1320...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1320 Nuclear uptake probe. (a) Identification. A nuclear uptake probe is a device intended to measure the amount of radionuclide taken up by...

  1. UPTAKE, TRANSLOCATION AND RELEASE OF PHOSPHORUS BY 'ELODEA DENSA'

    EPA Science Inventory

    Short-term (16h) laboratory studies of 32p uptake by Elodea densa rooted in sediment demonstrated both foliar and root uptake, and that translocation occurred acropetally and basipetally. Root absorption is projected to provide 83-85% of total phosphorus uptake during 12-16th pho...

  2. 21 CFR 868.1730 - Oxygen uptake computer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Oxygen uptake computer. 868.1730 Section 868.1730...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1730 Oxygen uptake computer. (a) Identification. An oxygen uptake computer is a device intended to compute the amount of oxygen consumed by...

  3. 21 CFR 868.1730 - Oxygen uptake computer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Oxygen uptake computer. 868.1730 Section 868.1730...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1730 Oxygen uptake computer. (a) Identification. An oxygen uptake computer is a device intended to compute the amount of oxygen consumed by...

  4. 21 CFR 868.1730 - Oxygen uptake computer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Oxygen uptake computer. 868.1730 Section 868.1730...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1730 Oxygen uptake computer. (a) Identification. An oxygen uptake computer is a device intended to compute the amount of oxygen consumed by...

  5. 21 CFR 868.1730 - Oxygen uptake computer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Oxygen uptake computer. 868.1730 Section 868.1730...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1730 Oxygen uptake computer. (a) Identification. An oxygen uptake computer is a device intended to compute the amount of oxygen consumed by...

  6. 21 CFR 868.1730 - Oxygen uptake computer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Oxygen uptake computer. 868.1730 Section 868.1730...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1730 Oxygen uptake computer. (a) Identification. An oxygen uptake computer is a device intended to compute the amount of oxygen consumed by...

  7. A thermodynamic formulation of root water uptake

    NASA Astrophysics Data System (ADS)

    Hildebrandt, A.; Kleidon, A.; Bechmann, M.

    2015-12-01

    By extracting bound water from the soil and lifting it to the canopy, root systems of vegetation perform work. Here we describe how the energetics involved in root water uptake can be quantified. The illustration is done using a simple, four-box model of the soil-root system to represent heterogeneity and a parameterization in which root water uptake is driven by the xylem potential of the plant with a fixed flux boundary condition. We use this approach to evaluate the effects of soil moisture heterogeneity and root system properties on the dissipative losses and export of energy involved in root water uptake. For this, we derive an expression that relates the energy export at the root collar to a sum of terms that reflect all fluxes and storage changes along the flow path in thermodynamic terms. We conclude that such a thermodynamic evaluation of root water uptake conveniently provides insights into the impediments of different processes along the entire flow path and explicitly accounting not only for the resistances along the flow path and those imposed by soil drying but especially the role of heterogenous soil water distribution. The results show that least energy needs to be exported and dissipative losses are minimized by a root system if it extracts water uniformly from the soil. This has implications for plant water relations in forests where canopies generate heterogenous input patterns. Our diagnostic in the energy domain should be useful in future model applications for quantifying how plants can evolve towards greater efficiency in their structure and function, particularly in heterogenous soil environments. Generally, this approach may help to better describe heterogeneous processes in the soil in a simple, yet physically-based way.

  8. Computer program for calculation of oxygen uptake

    NASA Technical Reports Server (NTRS)

    Castle, B. L.; Castle, G.; Greenleaf, J. E.

    1979-01-01

    A description and operational precedures are presented for a computer program, written in Super Basic, that calculates oxygen uptake, carbon dioxide production, and related ventilation parameters. Program features include: (1) the option of entering slope and intercept values of calibration curves for the O2 and CO2 and analyzers; (2) calculation of expired water vapor pressure; and (3) the option of entering inspured O2 and CO2 concentrations. The program is easily adaptable for programmable laboratory calculators.

  9. PARTITIONING THE RELATIVE INFLUENCE OF SOIL N, MYCORRHIZAE, AND FOLIAR N UPTAKE ON FOLIAR δ15N PATTERNS: CAN WE DETECT FOLIAR UPTAKE OF REACTIVE N?

    NASA Astrophysics Data System (ADS)

    Vallano, D.; Sparks, J. P.

    2009-12-01

    Vegetation is an important sink for atmospheric reactive N in N-limited systems and may be capable of incorporating reactive N compounds directly into leaves through the foliar uptake pathway. A proxy for atmospheric reactive N entering vegetation would be useful to estimate the impact of direct foliar N uptake on plant metabolism. Natural abundance foliar N isotopic composition (δ15N) is a practical tool for this purpose because plant-available N sources often have different isotopic compositions. Current understanding of foliar δ15N suggests these values primarily represent the integration of soil δ15N, direct foliar N uptake, mycorrhizal fractionation, and within-plant fractionations. Using a potted plant mesocosm system, we estimated the influence of mycorrhizae on foliar δ15N patterns in red maple (Acer rubrum) seedlings along an N deposition gradient in New York State. We found that mycorrhizal associations altered foliar δ15N in red maple seedlings from 0.03 - 1.01‰ across sites. Along the same temporal and spatial scales, we examined the influence of soil δ15N, foliar N uptake, and mycorrhizae on foliar δ15N in adult stands of American beech (Fagus grandifolia), black birch (Betula lenta), red maple (A. rubrum), and red oak (Quercus rubra). Using multiple regression models, atmospheric NO2 concentration explained 0%, 69%, 23%, and 45% of the residual variation in foliar δ15N remaining in American beech, red maple, red oak, and black birch, respectively, after accounting for soil δ15N. Our results suggest that foliar δ15N may be used to estimate pollution-derived atmospheric reactive N entering vegetation via the foliar N uptake pathway.

  10. Inhibitory action of sphingosine, sphinganine and dexamethasone on glucose uptake: Studies with hydrogen peroxide and phorbol ester

    SciTech Connect

    Murray, D.K.; Hill, M.E.; Nelson, D.H. )

    1990-01-01

    The mechanism of the inhibitory action of glucocorticoids on glucose uptake is incompletely understood. Treatment with corticosteriods of cells in which glucose uptake is stimulated at insulin postbinding and postreceptor sites may clarify the site of the steroid inhibitory action. Hydrogen peroxide, which has been shown to stimulate the insulin receptor tyrosine kinase, and phorbol myristate acetate (PMA) which stimulates protein kinase C were, therefore, used as stimulators of glucose transport in this study. These studies demonstrate that dexamethasone and the sphingoid bases, sphinganine and sphingosine, inhibit glucose uptake that has been stimulated at either the receptor kinase or protein kinase C level in both 3T3-L1 and 3T3-C2 cells. These data confirm glucocorticoid inhibitory action at a post binding level and support the suggestion that some corticosteriod inhibitory effects may be mediated by an action on sphingolipid metabolism.

  11. Water Uptake in PEMFC Catalyst Layers

    SciTech Connect

    Gunterman, Haluna P.; Kwong, Anthony H.; Gostick, Jeffrey T.; Kusoglu, Ahmet; Weber, Adam Z.

    2011-07-01

    Water uptake profiles of proton-exchange-membrane fuel-cell catalyst layers are characterized in the form of capillary-pressure saturation (Pc-S) curves. The curves indicate that the catalyst layers tested are highly hydrophilic and require capillary pressures as low as -80 kPa to eject imbibed water. Comparison of materials made with and without Pt indicates a difference in water ejection and uptake phenomena due to the presence of Pt. The addition of Pt increases the tendency of the catalyst layer to retain water. Dynamic vapor sorption (DVS) is used to characterize the water-vapor sorption onto Nafion, Pt/C, and C surfaces. The DVS results align with the trends found from the Pc-S curves and show an increased propensity for water uptake in the presence of Pt. The effect of the ion in Nafion, sodium or protonated form, is also compared and demonstrates that although the protonation of the Nafion in the catalyst layer also increases hydrophilicity, the effect is not as great as that caused by Pt.

  12. Light Conditions Affect the Measurement of Oceanic Bacterial Production via Leucine Uptake

    PubMed Central

    Morán, Xosé Anxelu G.; Massana, Ramon; Gasol, Josep M.

    2001-01-01

    The effect of irradiance in the range of 400 to 700 nm or photosynthetically active radiation (PAR) on bacterial heterotrophic production estimated by the incorporation of 3H-leucine (referred to herein as Leu) was investigated in the northwestern Mediterranean Sea and in a coastal North Atlantic site, with Leu uptake rates ranging over 3 orders of magnitude. We performed in situ incubations under natural irradiance levels of Mediterranean samples taken from five depths around solar noon and compared them to incubations in the dark. In two of the three stations large differences were found between light and dark uptake rates for the surfacemost samples, with dark values being on average 133 and 109% higher than in situ ones. Data obtained in coastal North Atlantic waters confirmed that dark enclosure may increase Leu uptake rates more than threefold. To explain these differences, on-board experiments of Leu uptake versus irradiance were performed with Mediterranean samples from depths of 5 and 40 m. Incubations under a gradient of 12 to 1,731 μmol of photons m−2 s−1 evidenced a significant increase in incorporation rates with increasing PAR in most of the experiments, with dark-incubated samples departing from this pattern. These results were not attributed to inhibition of Leu uptake in the light but to enhanced bacterial response when transferred to dark conditions. The ratio of dark to light uptake rates increased as dissolved inorganic nitrogen concentrations decreased, suggesting that bacterial nutrient deficiency was overcome by some process occurring only in the dark bottles. PMID:11525969

  13. Nitrogen deposition and prey nitrogen uptake control the nutrition of the carnivorous plant Drosera rotundifolia.

    PubMed

    Millett, J; Foot, G W; Svensson, B M

    2015-04-15

    Nitrogen (N) deposition has important negative impacts on natural and semi-natural ecosystems, impacting on biotic interactions across trophic levels. Low-nutrient systems are particularly sensitive to changes in N inputs and are therefore more vulnerable to N deposition. Carnivorous plants are often part of these ecosystems partly because of the additional nutrients obtained from prey. We studied the impact of N deposition on the nutrition of the carnivorous plant Drosera rotundifolia growing on 16 ombrotrophic bogs across Europe. We measured tissue N, phosphorus (P) and potassium (K) concentrations and prey and root N uptake using a natural abundance stable isotope approach. Our aim was to test the impact of N deposition on D. rotundifolia prey and root N uptake, and nutrient stoichiometry. D. rotundifolia root N uptake was strongly affected by N deposition, possibly resulting in reduced N limitation. The contribution of prey N to the N contained in D. rotundifolia ranged from 20 to 60%. N deposition reduced the maximum amount of N derived from prey, but this varied below this maximum. D. rotundifolia tissue N concentrations were a product of both root N availability and prey N uptake. Increased prey N uptake was correlated with increased tissue P concentrations indicating uptake of P from prey. N deposition therefore reduced the strength of a carnivorous plant-prey interaction, resulting in a reduction in nutrient transfer between trophic levels. We suggest that N deposition has a negative impact on D. rotundifolia and that responses to N deposition might be strongly site specific. PMID:25655989

  14. Molecular hydrogen uptake by soils in forest, desert, and marsh ecosystems in California

    NASA Astrophysics Data System (ADS)

    Smith-Downey, Nicole V.; Randerson, James T.; Eiler, John M.

    2008-09-01

    The mechanism and environmental controls on soil hydrogen (H2) uptake are not well understood but are essential for understanding the atmospheric H2 budget. Field observations of soil H2 uptake are limited, and here we present the results from a series of measurements in forest, desert, and marsh ecosystems in southern California. We measured soil H2 fluxes using flux chambers from September 2004 to July 2005. Mean H2 flux rates and standard deviations were -7.9 + -4.2, -7.6 + -5.3 and -7.5 + -3.4 nmol m-2 s-1 for the forest, desert, and marsh, respectively (corresponding to deposition velocities of 0.063 + -0.029, 0.051 + -0.036, 0.035 + -0.013 cm s-1). Soil profile measurements showed that H2 mixing ratios were between 3% and 51% of atmospheric levels at 10 cm and that the penetration of H2 into deeper soil layers increased with soil drying. Soil removal experiments in the forest demonstrated that the litter layer did not actively consume H2, the removal of this layer increased uptake by deeper soil layers, and the exposure of subsurface soil layers to ambient atmospheric H2 levels substantially increased their rate of uptake. Similar soil removal experiments at the desert site showed that extremely dry surface soils did not consume H2 and that fluxes at the surface increased when these inactive layers were removed. We present a model of soil H2 fluxes and show that the diffusivity of soils, along with the vertical distribution of layers that actively consume H2 regulate surface fluxes. We found that soil organic matter, CO2 fluxes, and ecosystem type were not strong controllers of H2 uptake. Our experiments highlight H2 diffusion into soils as an important limit on fluxes and that minimum moisture level is needed to initiate microbial uptake.

  15. Value siting

    SciTech Connect

    Ferrar, T.A.; Howes, J.A.

    1995-02-01

    Finding an appropriate site is becoming an increasing challenge in building new power projects. One of the first orders of business in project development is identifying a site that offers the maximum spread between the cost of fuel and net power price. The collection of sites that exhibit an adequate spread - presenting a first-order, acceptable economic expectation - must now be subjected to an ever increasing number of political, societal, technical, and economic exclusion screens. The barriers can include cooling water constraints, community resistance, visual incompatibility, archaeological concerns and endangered species preservation issues. Most power siting difficulties can be substantially mitigated by gaining access to developed, but under-used sites, whose current owners are bound by circumstances - political or financial - that prevent them from using such locations. There are two such categories of sites: Utilities that have sites on which depreciated power production assets rest; and, The federal government, with numerous sites throughout the country, particularly military bases subject to closure under the Base Realignment and Closure (BRAC) proceedings. It is in the interests of developers, as well as consumers, investors and taxpayers, ti undertake a thorough examination of these overlooked pearls of opportunities and develop their potential.

  16. Computational screening of iodine uptake in zeolitic imidazolate frameworks in a water-containing system.

    PubMed

    Yuan, Yue; Dong, Xiuqin; Chen, Yifei; Zhang, Minhua

    2016-08-17

    Iodine capture is of great environmental significance due to the high toxicity and volatility of I2. Here we conduct a systematic computational investigation of iodine adsorption in zeolitic imidazolate frameworks (ZIFs) by adopting the grand canonical Monte Carlo (GCMC) simulation and the density functional theory (DFT) method. The results confirm the vital structural factors for iodine adsorption at 298 K and moderate pressures including metal sites, organic linkers, symmetry, and topology types. The uptake will be enhanced by active metal sites, the simple imidazolate linker and single asymmetric linkers with polar functional groups. The symmetry effect is stronger than the surface properties. Meanwhile low steric hindrance is more beneficial than polar functional groups to iodine adsorption. The specific topology types like mer bringing large surface areas and large diameter cages result in high iodine capacities. Iodine molecules tend to locate in cages with large diameters and aggregates along the sides of cages. In contrast, water prefers small diameter cages. In hydrophilic materials, water has a negative impact on iodine uptake due to its similar adsorption sites to iodine. The selectivity of iodine over water increases with increasing water content due to the large diameter cages of ZIFs. This work proves that ZIFs can be identified as efficient and economical adsorbents with high diversity for iodine in a water-containing system. Furthermore, it provides comprehensive insights into key structural factors for iodine uptake and separation in silver-free porous solids. PMID:27499079

  17. Repetitive mechanical strain suppresses macrophage uptake of immunoglobulin G complexes and enhances cyclic adenosine monophosphate synthesis.

    PubMed Central

    Mattana, J.; Sankaran, R. T.; Singhal, P. C.

    1995-01-01

    Uptake of immunoglobulin G (IgG) complexes by macrophages (M phi) may play an important role in disease states characterized by increased levels of circulating immune complexes. In sites such as the glomerular mesangium M phi may be subjected to repetitive mechanical strain, although in vitro studies of M phi endocytosis are typically carried out with cells grown on rigid surfaces. We undertook the present study to determine whether repetitive mechanical strain could modulate M phi endocytosis of IgG complexes. IgG complex uptake was significantly diminished in M phi that were subjected to repetitive mechanical strain using parameters corresponding to peak and minimal intraglomerular pressures compared with control, and uptake varied according to the amount of mechanical strain applied. There was no significant difference in surface binding of IgG between M phi subjected to strain and those not. Mechanical strain did not significantly influence the rate of IgG complex degradation. Inhibition of nitric oxide synthase and guanylate cyclase activity did not alter the effect of mechanical strain, although this effect was potentiated by 3-isobutyl-1-methylxanthine (IBMX). Angiotensin II, which has been shown to reduce adenosine 3',5'-cyclic monophosphate (cAMP) production in M phi, significantly attenuated the suppressive effect of mechanical strain on IgG complex uptake as well as another inhibitor of cAMP generation, indomethacin. Enzyme immunoassay demonstrated significantly enhanced levels of cAMP in M phi that were subjected to mechanical strain compared with control, an effect that was potentiated by IBMX and attenuated by angiotensin II and indomethacin. These results demonstrate that repetitive mechanical strain significantly reduces IgG complex uptake by M phi, most likely by enhancing cAMP synthesis. Such an effect might play a significant role in macromolecule handling by M phi in sites in which they are subjected to repetitive mechanical deformation such as

  18. Modelling water uptake efficiency of root systems

    NASA Astrophysics Data System (ADS)

    Leitner, Daniel; Tron, Stefania; Schröder, Natalie; Bodner, Gernot; Javaux, Mathieu; Vanderborght, Jan; Vereecken, Harry; Schnepf, Andrea

    2016-04-01

    Water uptake is crucial for plant productivity. Trait based breeding for more water efficient crops will enable a sustainable agricultural management under specific pedoclimatic conditions, and can increase drought resistance of plants. Mathematical modelling can be used to find suitable root system traits for better water uptake efficiency defined as amount of water taken up per unit of root biomass. This approach requires large simulation times and large number of simulation runs, since we test different root systems under different pedoclimatic conditions. In this work, we model water movement by the 1-dimensional Richards equation with the soil hydraulic properties described according to the van Genuchten model. Climatic conditions serve as the upper boundary condition. The root system grows during the simulation period and water uptake is calculated via a sink term (after Tron et al. 2015). The goal of this work is to compare different free software tools based on different numerical schemes to solve the model. We compare implementations using DUMUX (based on finite volumes), Hydrus 1D (based on finite elements), and a Matlab implementation of Van Dam, J. C., & Feddes 2000 (based on finite differences). We analyse the methods for accuracy, speed and flexibility. Using this model case study, we can clearly show the impact of various root system traits on water uptake efficiency. Furthermore, we can quantify frequent simplifications that are introduced in the modelling step like considering a static root system instead of a growing one, or considering a sink term based on root density instead of considering the full root hydraulic model (Javaux et al. 2008). References Tron, S., Bodner, G., Laio, F., Ridolfi, L., & Leitner, D. (2015). Can diversity in root architecture explain plant water use efficiency? A modeling study. Ecological modelling, 312, 200-210. Van Dam, J. C., & Feddes, R. A. (2000). Numerical simulation of infiltration, evaporation and shallow

  19. Modeling vapor uptake induced mobility shifts in peptide ions observed with transversal modulation ion mobility spectrometry-mass spectrometry.

    PubMed

    Rawat, Vivek K; Vidal-de-Miguel, Guillermo; Hogan, Christopher J

    2015-10-21

    Low field ion mobility spectrometry-mass spectrometry (IMS-MS) techniques exhibit low orthogonality, as inverse mobility often scales with mass to charge ratio. This inadequacy can be mitigated by adding vapor dopants, which may cluster with analyte ions and shift their mobilities by amounts independent of both mass and mobility of the ion. It is therefore important to understand the interactions of vapor dopants with ions, to better quantify the extent of dopant facilitated mobility shifts. Here, we develop predictive models of vapor dopant facilitated mobility shifts, and compare model calculations to measurements of mobility shifts for peptide ions exposed to variable gas phase concentrations of isopropanol. Mobility measurements were made at atmospheric pressure and room temperature using a recently developed transversal modulation ion mobility spectrometer (TMIMS). Results are compared to three separate models, wherein mobility shifts due to vapor dopants are attributed to changes in gas composition and (I) no vapor dopant uptake is assumed, (II) site-specific dopant uptake by the ion is assumed (approximated via a Langmuir adsorption model), and (III) site-unspecific dopant uptake by the ion is assumed (approximated via a classical nucleation model). We find that mobility shifts in peptide ions are in excellent agreement with model II, site-specific binding predictions. Conversely, mobility shifts of tetraalkylammonium ions from previous measurements were compared with these models and best agreement was found with model III predictions, i.e. site-unspecific dopant uptake. PMID:26051323

  20. Monitoring vegetation water uptake in a semiarid riparian corridor

    NASA Astrophysics Data System (ADS)

    Robinson, J.; Ochoa, C. G.; Leonard, J.

    2015-12-01

    With a changing global climate and growing demand for water throughout the world, responsible and sustainable land and water resource management practices are becoming increasingly important. Accounting for the amount of water used by riparian vegetation is a critical element for better managing water resources in arid and semiarid environments. The objective of this study was to determine water uptake by selected riparian vegetative species in a semiarid riparian corridor in North-Central Oregon. Exo-skin sap flow sensors (Dynamax, Houston, TX, U.S.A.) were used to measure sap flux in red alder (Alnus rubra) trees, the dominant overstory vegetation at the field site. Xylem sap flow data was collected from selected trees at the field site and in a greenhouse setting. Transpiration rates were determined based on an energy balance method, which makes it possible to estimate the mass flow of sap by measuring the velocity of electrical heat pulses through the plant stem. Preliminary field results indicate that red alder tree branches of about 1 inch diameter transpire between 2 and 6 kg of water/day. Higher transpiration rates of up to 7.3 kg of water/day were observed under greenhouse conditions. Streamflow and stream water temperature, vegetation characteristics, and meteorological data were analyzed in conjunction with transpiration data. Results of this study provide insight on riparian vegetation water consumption in water scarce ecosystems. This study is part of an overarching project focused on climate-vegetation interactions and ecohydrologic processes in arid and semiarid landscapes.

  1. Cloning and characterization of hydrogen uptake genes from Rhizobium leguminosarum.

    PubMed Central

    Leyva, A; Palacios, J M; Mozo, T; Ruiz-Argüeso, T

    1987-01-01

    A gene library of genomic DNA from the hydrogen uptake (Hup)-positive strain 128C53 of Rhizobium leguminosarum was constructed by using the broad-host-range mobilizable cosmid vector pLAFR1. The resulting recombinant cosmids contained insert DNA averaging 21 kilobase pairs (kb) in length. Two clones from the above gene library were identified by colony hybridization with DNA sequences from plasmid pHU1 containing hup genes of Bradyhizobium japonicum. The corresponding recombinant cosmids, pAL618 and pAL704, were isolated, and a region of about 28 kb containing the sequences homologous to B. japonicum hup-specific DNA was physically mapped. Further hybridization analysis with three fragments from pHU1 (5.9-kb HindIII, 2.9-kb EcoRI, and 5.0-kb EcoRI) showed that the overall arrangement of the R. leguminosarum hup-specific region closely parallels that of B. japonicum. The presence of functional hup genes within the isolated cosmid DNA was demonstrated by site-directed Tn5 mutagenesis of the 128C53 genome and analysis of the Hup phenotype of the Tn5 insertion strains in symbiosis with peas. Transposon Tn5 insertions at six different sites spanning 11 kb of pAL618 completely suppressed the hydrogenase activity of the pea bacteroids. Images PMID:2822654

  2. Characterization of Iron Uptake from Ferrioxamine B by Chlorella vulgaris

    PubMed Central

    Allnutt, F. C. Thomas; Bonner, Walter D.

    1987-01-01

    Iron uptake from two Fe3+-hydroxamate siderophores, ferrioxamine B and Fe3+-rhodotorulate, by iron-stressed Chlorella vulgaris (ATCC strain 11468) was evaluated with some comparison to iron uptake from synthetic and organic acid ferric chelates. Iron-stress induced iron uptake from ferrioxamine B. Dissipation of the electrochemical gradient, via uncouplers, inhibited iron uptake. Respiratory inhibitors gave variable results, an indication that a direct link to respiration was not apparent. Vanadate inhibition of iron uptake indicated that an ATPase or phosphate intermediate could be involved in the uptake mechanism. Divalent cations manifested variable effects dependent on the cation and chelator used. These data confirm that C. vulgaris has an inducible iron-uptake system for Fe3+-hydroxamic acid siderophores which may involve a different mechanism than that observed for other chelates. PMID:16665771

  3. Antihistamine effect on synaptosomal uptake of serotonin, norepinephrine and dopamine

    NASA Technical Reports Server (NTRS)

    Brown, P. A.; Vernikos, J.

    1980-01-01

    A study on the effects of five H1 and H2 antihistamines on the synaptosomal uptake of serotonin (5HT), norepinephrine (NE), and dopamine (DA) is presented. Brain homogenates from female rats were incubated in Krebs-Ringer phosphate buffer solution in the presence of one of three radioactive neurotransmitters, and one of the five antihistamines. Low concentrations of pyrilamine competitively inhibited 5HT uptake, had little effect on NE uptake, and no effect on DA uptake. Promethazine, diphenhydramine, metiamide, and cimetidine had no effect on 5HT or DA uptake at the same concentration. Diphenhydramine had a small inhibitory effect on NE uptake. It is concluded that pyrilamine is a selective and potent competitive inhibitor of 5HT uptake at concentrations between .05 and .5 micromolars.

  4. A primary fish gill cell culture model to assess pharmaceutical uptake and efflux: evidence for passive and facilitated transport.

    PubMed

    Stott, Lucy C; Schnell, Sabine; Hogstrand, Christer; Owen, Stewart F; Bury, Nic R

    2015-02-01

    The gill is the principle site of xenobiotic transfer to and from the aqueous environment. To replace, refine or reduce (3Rs) the large numbers of fish used in in vivo uptake studies an effective in vitro screen is required that mimics the function of the teleost gill. This study uses a rainbow trout (Oncorhynchus mykiss) primary gill cell culture system grown on permeable inserts, which tolerates apical freshwater thus mimicking the intact organ, to assess the uptake and efflux of pharmaceuticals across the gill. Bidirectional transport studies in media of seven pharmaceuticals (propranolol, metoprolol, atenolol, formoterol, terbutaline, ranitidine and imipramine) showed they were transported transcellularly across the epithelium. However, studies conducted in water showed enhanced uptake of propranolol, ranitidine and imipramine. Concentration-equilibrated conditions without a concentration gradient suggested that a proportion of the uptake of propranolol and imipramine is via a carrier-mediated process. Further study using propranolol showed that its transport is pH-dependent and at very low environmentally relevant concentrations (ng L(-1)), transport deviated from linearity. At higher concentrations, passive uptake dominated. Known inhibitors of drug transport proteins; cimetidine, MK571, cyclosporine A and quinidine inhibited propranolol uptake, whilst amantadine and verapamil were without effect. Together this suggests the involvement of specific members of SLC and ABC drug transporter families in pharmaceutical transport. PMID:25544062

  5. A primary fish gill cell culture model to assess pharmaceutical uptake and efflux: Evidence for passive and facilitated transport

    PubMed Central

    Stott, Lucy C.; Schnell, Sabine; Hogstrand, Christer; Owen, Stewart F.; Bury, Nic R.

    2015-01-01

    The gill is the principle site of xenobiotic transfer to and from the aqueous environment. To replace, refine or reduce (3Rs) the large numbers of fish used in in vivo uptake studies an effective in vitro screen is required that mimics the function of the teleost gill. This study uses a rainbow trout (Oncorhynchus mykiss) primary gill cell culture system grown on permeable inserts, which tolerates apical freshwater thus mimicking the intact organ, to assess the uptake and efflux of pharmaceuticals across the gill. Bidirectional transport studies in media of seven pharmaceuticals (propranolol, metoprolol, atenolol, formoterol, terbutaline, ranitidine and imipramine) showed they were transported transcellularly across the epithelium. However, studies conducted in water showed enhanced uptake of propranolol, ranitidine and imipramine. Concentration-equilibrated conditions without a concentration gradient suggested that a proportion of the uptake of propranolol and imipramine is via a carrier-mediated process. Further study using propranolol showed that its transport is pH-dependent and at very low environmentally relevant concentrations (ng L−1), transport deviated from linearity. At higher concentrations, passive uptake dominated. Known inhibitors of drug transport proteins; cimetidine, MK571, cyclosporine A and quinidine inhibited propranolol uptake, whilst amantadine and verapamil were without effect. Together this suggests the involvement of specific members of SLC and ABC drug transporter families in pharmaceutical transport. PMID:25544062

  6. Elevated Uptake of Plasma Macromolecules by Regions of Arterial Wall Predisposed to Plaque Instability in a Mouse Model

    PubMed Central

    Mohri, Zahra; Rowland, Ethan M.; Clarke, Lindsey A.; De Luca, Amalia; Peiffer, Véronique; Krams, Rob; Sherwin, Spencer J.; Weinberg, Peter D.

    2014-01-01

    Atherosclerosis may be triggered by an elevated net transport of lipid-carrying macromolecules from plasma into the arterial wall. We hypothesised that whether lesions are of the thin-cap fibroatheroma (TCFA) type or are less fatty and more fibrous depends on the degree of elevation of transport, with greater uptake leading to the former. We further hypothesised that the degree of elevation can depend on haemodynamic wall shear stress characteristics and nitric oxide synthesis. Placing a tapered cuff around the carotid artery of apolipoprotein E -/- mice modifies patterns of shear stress and eNOS expression, and triggers lesion development at the upstream and downstream cuff margins; upstream but not downstream lesions resemble the TCFA. We measured wall uptake of a macromolecular tracer in the carotid artery of C57bl/6 mice after cuff placement. Uptake was elevated in the regions that develop lesions in hyperlipidaemic mice and was significantly more elevated where plaques of the TCFA type develop. Computational simulations and effects of reversing the cuff orientation indicated a role for solid as well as fluid mechanical stresses. Inhibiting NO synthesis abolished the difference in uptake between the upstream and downstream sites. The data support the hypothesis that excessively elevated wall uptake of plasma macromolecules initiates the development of the TCFA, suggest that such uptake can result from solid and fluid mechanical stresses, and are consistent with a role for NO synthesis. Modification of wall transport properties might form the basis of novel methods for reducing plaque rupture. PMID:25531765

  7. Effects of calmodulin and calmodulin inhibitors on Ca uptake by sarcoplasmic reticulum of saponin skinned caudal artery

    SciTech Connect

    Stout, M.A.; Silver, P.J.

    1986-03-05

    Calmodulin (CaM) stimulates plasma membrane transport in many cell types, however, its role in Ca regulation by the sarcoplasmic reticulum (SR) in smooth muscle has not been established. /sup 45/Ca uptake was studied in saponin skinned strips of rat caudal artery as a function of CaM and the CaM inhibitors, W-7, calmidazolium (CaMZ), and trifluoperazine (TFP). Although caudal artery strips lose approximately 30% of total tissue CaM during skinning, 0.3 - 2 ..mu..M CaM did not increase /sup 45/Ca uptake over a wide range of free Ca concentrations (10/sup -8/ - 10/sup -6/M). Neither W-7 nor CaMZ at concentration of 10/sup -4/ - 2 x 10/sup -4/M inhibited the MgATP-dependent Ca uptake. Ca uptake was not affected by 50 ..mu..M TFP but a significant inhibition was produced by 500 ..mu..M. Studies of the effects of TFP on /sup 45/Ca efflux indicated that TFP concentrations which inhibited Ca uptake also significantly increased the rate of Ca release. The results suggest that total Ca uptake in caudal artery depends mainly upon MgATP and is not modulated by exogenous CaM or affected by these CaM inhibitors. They cannot preclude that CaM may affect initial velocities or that the CaM inhibitors failed to reach active sites.

  8. Influence of soil structure on unsaturated water flow including root uptake

    NASA Astrophysics Data System (ADS)

    Kuhlmann, Anna; Neuweiler, Insa; van der Zee, Sjoerd; Helmig, Rainer

    2010-05-01

    The development of effective irrigation strategies is of great importance as the scarcity of water during extended dry periods in aride areas leads to limited water uptake by roots and thus to restricted growth and eventually to wilting of plants. To approach this goal a broad understanding of the factors which influence the distribution of the water potential and the interactions with root uptake is crucial. Soil structure is supposed to have a large impact on water flow especially under dry conditions when the variability of soil parameters is increased. For field applications, predictions of the water flow are needed for large scales where the scarcity of measurements leads to a high level of uncertainty about the detailed distribution of soil parameters. Thus stochastic methods in which heterogeneity of soil is described by a random parameter field are used. In this presentation, the interrelation of root uptake and heterogeneity is analyzed using numerical simulations. Random parameter fields with Gaussian and non-Gaussian dependence were parameterized according to the Las Cruces Trench Site dataset and used as input for the numerical model. Transpiration is considered in a macroscopic way as a sink term with a prescribed potential extraction rate at each node, determined by the density distribution of the plants and with restricted uptake due to unfavorable conditions as lack of water and oxygen (modeled according to the Feddes - Function). With this basic model, water flow in two dimensional random fields has been investigated under dry conditions. It was observed that dry spots - regions in which roots dry up to the wilting point form when the structure shows isolated high extreme values in conductivity. In these dry regions, roots take up a decreased amount of water such that the total potential demand is not met anymore. This seems rather unrealistic as sufficient water is available at other locations of the domain. Thus two other approaches are analyzed

  9. First respiration estimates of cold-seep vesicomyid bivalves from in situ total oxygen uptake measurements.

    PubMed

    Decker, Carole; Caprais, Jean-Claude; Khripounoff, Alexis; Olu, Karine

    2012-04-01

    Vesicomyid bivalves are one of the most abundant symbiont-bearing species inhabiting deep-sea reducing ecosystems. Nevertheless, except for the hydrothermal vent clam Calyptogena magnifica, their metabolic rates have not been documented, and only assessed with ex situ experiments. In this study, gathering benthic chamber measurements and biomass estimation, we give the first in situ assessment of the respiration rate of these bivalves. The giant pockmark Regab, located at 3160m depth along the Congo-Angola margin, is a cold-seep site characterised by dense assemblages of two species of vesicomyids: Christineconcha regab and Laubiericoncha chuni with high dominance of C. regab. Two sites with dense aggregates of vesicomyids were selected to measure total oxygen uptake (TOU), and methane fluxes using IFREMER's benthic chamber CALMAR deployed by the ROV Quest 4000 (MARUM). Photographs were taken and bivalves were sampled using blade corers to estimate density and biomass. Total oxygen uptake was higher at Site 2 compared to Site 1 (respectively 492 mmol.m(-2).d(-1) and 332 mmol.m(-2).d(-1)). However, given vesicomyid densities and biomass, mean oxygen consumption rates were similar at both sites (1.9 to 2.5 μmol.g total dry mass(-1).h(-1) at the Site 1 and 1.8 to 2.3 μmol.g total dry mass(-1).h(-1) at Site 2). These respiration rates are higher than published ex situ estimates for cold-seep or hydrothermal vent bivalves. Although methane fluxes at the base of sulphide production were clearly higher at Site 2 (14.6 mmol.m(-2).d(-1)) than at Site 1 (0.3 mmol.m(-2).d(-1)), they do not seem to influence the respiration rates of these bivalves associated to sulphide-oxidizing symbionts. PMID:22578572

  10. Uptake of Mass Drug Administration Programme for Schistosomiasis Control in Koome Islands, Central Uganda

    PubMed Central

    Tuhebwe, Doreen; Bagonza, James; Kiracho, Elizabeth Ekirapa; Yeka, Adoke; Elliott, Alison M.; Nuwaha, Fred

    2015-01-01

    Introduction Schistosomiasis is one of the neglected tropical diseases targeted for elimination in Uganda through the Mass Drug Administration (MDA) programme. Praziquantel has been distributed using community resource persons in fixed sites and house-to-house visits; however the uptake is still below target coverage. In 2011/2012 MDA exercise, uptake stood at 50% yet WHO target coverage is 75% at community level. We assessed the uptake of MDA and the associated factors in Koome Islands, Central Uganda. Methods In March 2013, we conducted a mixed methods cross sectional study in 15 randomly selected villages. We interviewed a total of 615 respondents aged 18 years and above using semi structured questionnaires and five key informants were also purposively selected. Univariate and multivariate analysis was done. MDA uptake was defined as self reported swallowing of praziquantel during the last (2012) MDA campaign. We conducted key informant interviews with Ministry of Health, district health personnel and community health workers. Results Self reported uptake of praziquantel was 44.7% (275/615), 95% confidence interval (CI) 40.8–48.7%. Of the 275 community members who said they had swallowed praziquantel, 142 (51.6%) reported that they had developed side effects. Uptake of MDA was more likely if the respondent was knowledgeable about schistosomiasis transmission and prevention (adjusted odds ratio [AOR] 1.85, 95% CI 1.22–2.81) and reported to have received health education from the health personnel (AOR 5.95, 95% CI 3.67–9.65). Service delivery challenges such as drug shortages and community health worker attrition also influenced MDA in Koome Islands. Conclusions Uptake of MDA for schistosomiasis control in Koome was sub optimal. Lack of knowledge about schistosomiasis transmission and prevention, inadequate health education and drug shortages are some of the major factors associated with low uptake. These could be addressed through routine health education

  11. Assessment of plant uptake models used in exposure assessment tools for soils contaminated with organic pollutants.

    PubMed

    Takaki, Koki; Wade, Andrew J; Collins, Chris D

    2014-10-21

    The aim of this study was to evaluate and improve the accuracy of plant uptake models for neutral hydrophobic organic pollutants (1 < logK(OW) < 9, -8 < logK(AW) < 0) used in regulatory exposure assessment tools, using uncertainty and sensitivity analyses. The models considered were RAIDAR, EUSES, CSOIL, CLEA, and CalTOX. In this research, CSOIL demonstrated the best performance of all five exposure assessment tools for root uptake from polluted soil in comparison with observed data, but no model predicted shoot uptake well. Recalibration of the transpiration and volatilisation parameters improved the performance of CSOIL and CLEA. The dominant pathway for shoot uptake simulated differed according to the properties of the chemical under consideration; those with a higher air-water partition coefficient were transported into shoots via the soil-air-plant pathway, while chemicals with a lower octanol-water partition coefficient and air-water partition coefficient were transported via the root. The soil organic carbon content was a particularly sensitive parameter in each model and using a site specific value improved model performance. PMID:25203369

  12. Modeling the uptake and transpiration of TCE using phreatophytic trees. Master`s Thesis

    SciTech Connect

    Wise, D.P.

    1997-12-01

    Phytoremediation is a recent addition to the numerous methods used today to remediate ground water contaminants. It is proving more effective and efficient compared to existing remediation techniques. The use of phreatophytes, or water seeking trees, has great potential for phytoremediation. These trees are fast growing, long lived, grow their roots down to the ground water table, transpire large amounts of water, and are proven to actively remove contaminants from the soil horizon. The purpose of this research is to develop quantitative concepts for understanding the dynamics of TCE uptake and transpiration by phreatophytic trees over a short rotation woody crop time frame. This will he done by constructing a system dynamics model of this process and running it over a wide range of conditions. This research will offer managers a tool to simulate long-term uptake and transpiration of TCE at potential sites. The results of this study indicate that TCE is actively removed from the soil horizon by phreatophytic trees and a significant proportion of this TCE is then transpired. Changes in soil horizon parameters, xylem flow rates, and variables in the uptake equation greatly influence TCE uptake rates as well as transpiration. Also, parameters used in equations representing flows in and out of the leaf greatly influence transpiration. Better understanding of these processes is essential for managers to accurately predict the amount of TCE removed and transpired during potential phytoremediation projects.

  13. Uptake of uranium from seawater by amidoxime-based polymeric adsorbent marine testing

    SciTech Connect

    Tsouris, C.; Kim, J.; Oyola, Y.; Mayes, R.; Hexel, C.; Sostre Gonzalez, F.; Janke, C.; Dai, S.; Gill, G.; Kuo, L.J.; Wood, J.; Choe, K.Y.; Pourmand, A.; D'Alessandro, E.; Buesseler, K.; Pike, S.

    2013-07-01

    Amidoxime-based polymer adsorbents in the form of functionalized fibers were prepared at the Oak Ridge National Laboratory (ORNL) and screened in laboratory experiments, in terms of uranium uptake capacity, using spiked uranium solution and seawater samples. Batch laboratory experiments conducted with 5-gallon seawater tanks provided equilibrium information. Based on results from 5-gallon experiments, the best adsorbent was selected for field-testing of uranium adsorption from seawater. Flow-through column tests have been performed at different marine sites to investigate the uranium uptake rate and equilibrium capacity under diverse biogeochemistry. The maximum amount of uranium uptake from seawater tests at Sequim, WA, was 3.3 mg U/g adsorbent after eight weeks of contact of the adsorbent with seawater. This amount was three times higher than the maximum adsorption capacity achieved in this study by a leading adsorbent developed by the Japan Atomic Energy Agency (JAEA), which was 1.1 mg U/g adsorbent at equilibrium. The initial uranium uptake rate of the ORNL adsorbent was 2.6 times higher than that of the JAEA adsorbent under similar conditions. A mathematical model derived from the mass balance of uranium was employed to describe the data. (authors)

  14. Characterization of OpdH, a Pseudomonas aeruginosa Porin Involved in the Uptake of Tricarboxylates▿

    PubMed Central

    Tamber, Sandeep; Maier, Elke; Benz, Roland; Hancock, Robert E. W.

    2007-01-01

    The Pseudomonas aeruginosa outer membrane is intrinsically impermeable to many classes of antibiotics, due in part to its relative lack of general uptake pathways. Instead, this organism relies on a large number of substrate-specific uptake porins. Included in this group are the 19 members of the OprD family, which are involved in the uptake of a diverse array of metabolites. One of these porins, OpdH, has been implicated in the uptake of cis-aconitate. Here we demonstrate that this porin may also enable P. aeruginosa to take up other tricarboxylates. Isocitrate and citrate strongly and specifically induced the opdH gene via a mechanism involving derepression by the putative two-component regulatory system PA0756-PA0757. Planar bilayer analysis of purified OpdH demonstrated that it was a channel-forming protein with a large single-channel conductance (230 pS in 1 M KCl; 10-fold higher than that of OprD); however, we were unable to demonstrate the presence of a tricarboxylate binding site within the channel. Thus, these data suggest that the requirement for OpdH for efficient growth on tricarboxylates was likely due to the specific expression of this large-channel porin under particular growth conditions. PMID:17114261

  15. An Actin Filament Population Defined by the Tropomyosin Tpm3.1 Regulates Glucose Uptake

    PubMed Central

    Kee, Anthony J.; Yang, Lingyan; Lucas, Christine A.; Greenberg, Michael J.; Martel, Nick; Leong, Gary M.; Hughes, William E.; Cooney, Gregory J.; James, David E.; Ostap, E. Michael; Han, Weiping; Gunning, Peter W.; Hardeman, Edna C.

    2016-01-01

    Actin has an ill-defined role in the trafficking of GLUT4 glucose transporter vesicles to the plasma membrane (PM). We have identified novel actin filaments defined by the tropomyosin Tpm3.1 at glucose uptake sites in white adipose tissue (WAT) and skeletal muscle. In Tpm 3.1-overexpressing mice, insulin-stimulated glucose uptake was increased; while Tpm3.1-null mice they were more sensitive to the impact of high-fat diet on glucose uptake. Inhibition of Tpm3.1 function in 3T3-L1 adipocytes abrogates insulin-stimulated GLUT4 translocation and glucose uptake. In WAT, the amount of filamentous actin is determined by Tpm3.1 levels and is paralleled by changes in exocyst component (sec8) and Myo1c levels. In adipocytes, Tpm3.1 localizes with MyoIIA, but not Myo1c, and it inhibits Myo1c binding to actin. We propose that Tpm3.1 determines the amount of cortical actin that can engage MyoIIA and generate contractile force, and in parallel limits the interaction of Myo1c with actin filaments. The balance between these actin filament populations may determine the efficiency of movement and/or fusion of GLUT4 vesicles with the PM. PMID:25783006

  16. A Comparative Study of Iron Uptake Rates and Mechanisms amongst Marine and Fresh Water Cyanobacteria: Prevalence of Reductive Iron Uptake

    PubMed Central

    Lis, Hagar; Kranzler, Chana; Keren, Nir; Shaked, Yeala

    2015-01-01

    In this contribution, we address the question of iron bioavailability to cyanobacteria by measuring Fe uptake rates and probing for a reductive uptake pathway in diverse cyanobacterial species. We examined three Fe-substrates: dissolved inorganic iron (Fe') and the Fe-siderophores Ferrioxamine B (FOB) and FeAerobactin (FeAB). In order to compare across substrates and strains, we extracted uptake rate constants (kin = uptake rate/[Fe-substrate]). Fe' was the most bioavailable Fe form to cyanobacteria, with kin values higher than those of other substrates. When accounting for surface area (SA), all strains acquired Fe' at similar rates, as their kin/SA were similar. We also observed homogeneity in the uptake of FOB among strains, but with 10,000 times lower kin/SA values than Fe'. Uniformity in kin/SA suggests similarity in the mechanism of uptake and indeed, all strains were found to employ a reductive step in the uptake of Fe' and FOB. In contrast, different uptake pathways were found for FeAB along with variations in kin/SA. Our data supports the existence of a common reductive Fe uptake pathway amongst cyanobacteria, functioning alone or in addition to siderophore-mediated uptake. Cyanobacteria combining both uptake strategies benefit from increased flexibility in accessing different Fe-substrates. PMID:25768677

  17. Antigen Uptake during Different Life Stages of Zebrafish (Danio rerio) Using a GFP-Tagged Yersinia ruckeri.

    PubMed

    Korbut, Rozalia; Mehrdana, Foojan; Kania, Per Walter; Larsen, Marianne Halberg; Frees, Dorte; Dalsgaard, Inger; Jørgensen, Louise von Gersdorff

    2016-01-01

    Immersion-vaccines (bacterins) are routinely used for aquacultured rainbow trout to protect against Yersinia ruckeri (Yr). During immersion vaccination, rainbow trout take up and process the antigens, which induce protection. The zebrafish was used as a model organism to study uptake mechanisms and subsequent antigen transport in fish. A genetically modified Yr was developed to constitutively express green fluorescent protein (GFP) and was used for bacterin production. Larval, juvenile and adult transparent zebrafish (tra:nac mutant) received a bath in the bacterin for up to 30 minutes. Samples were taken after 1 min, 15 min, 30 min, 2 h, 12 h and 24 h. At each sampling point fish were used for live imaging of the uptake using a fluorescence stereomicroscope and for immunohistochemistry (IHC). In adult fish, the bacterin could be traced within 30 min in scale pockets, skin, oesophagus, intestine and fins. Within two hours post bath (pb) Yr-antigens were visible in the spleen and at 24 h in liver and kidney. Bacteria were associated with the gills, but uptake at this location was limited. Antigens were rarely detected in the blood and never in the nares. In juvenile fish uptake of the bacterin was seen in the intestine 30 min pb and in the nares 2 hpb but never in scale pockets. Antigens were detected in the spleen 12 hpb. Zebrafish larvae exhibited major Yr uptake only in the mid-intestine enterocytes 24 hpb. The different life stages of zebrafish varied with regard to uptake locations, however the gut was consistently a major uptake site. Zebrafish and rainbow trout tend to have similar uptake mechanisms following immersion or bath vaccination, which points towards zebrafish as a suitable model organism for this aquacultured species. PMID:27404564

  18. Antigen Uptake during Different Life Stages of Zebrafish (Danio rerio) Using a GFP-Tagged Yersinia ruckeri

    PubMed Central

    Korbut, Rozalia; Mehrdana, Foojan; Kania, Per Walter; Larsen, Marianne Halberg; Frees, Dorte; Dalsgaard, Inger; Jørgensen, Louise von Gersdorff

    2016-01-01

    Immersion-vaccines (bacterins) are routinely used for aquacultured rainbow trout to protect against Yersinia ruckeri (Yr). During immersion vaccination, rainbow trout take up and process the antigens, which induce protection. The zebrafish was used as a model organism to study uptake mechanisms and subsequent antigen transport in fish. A genetically modified Yr was developed to constitutively express green fluorescent protein (GFP) and was used for bacterin production. Larval, juvenile and adult transparent zebrafish (tra:nac mutant) received a bath in the bacterin for up to 30 minutes. Samples were taken after 1 min, 15 min, 30 min, 2 h, 12 h and 24 h. At each sampling point fish were used for live imaging of the uptake using a fluorescence stereomicroscope and for immunohistochemistry (IHC). In adult fish, the bacterin could be traced within 30 min in scale pockets, skin, oesophagus, intestine and fins. Within two hours post bath (pb) Yr-antigens were visible in the spleen and at 24 h in liver and kidney. Bacteria were associated with the gills, but uptake at this location was limited. Antigens were rarely detected in the blood and never in the nares. In juvenile fish uptake of the bacterin was seen in the intestine 30 min pb and in the nares 2 hpb but never in scale pockets. Antigens were detected in the spleen 12 hpb. Zebrafish larvae exhibited major Yr uptake only in the mid-intestine enterocytes 24 hpb. The different life stages of zebrafish varied with regard to uptake locations, however the gut was consistently a major uptake site. Zebrafish and rainbow trout tend to have similar uptake mechanisms following immersion or bath vaccination, which points towards zebrafish as a suitable model organism for this aquacultured species. PMID:27404564

  19. Fallout of lead and uptake by crops

    NASA Astrophysics Data System (ADS)

    Chamberlain, A. C.

    The distribution with depth of lead in cores of peat shows that the annual fallout in the U.K. has not changed greatly since the middle of the last century. Increased fallout of lead from vehicles has been balanced by decreases in other sources. Fallout of lead from vehicles since 1946 has contributed about 3 ppm in country districts and less than 10 ppm in towns to topsoils. This represents a small addition to the amounts naturally present or attributable to dissemination of industrial and domestic waste over the centuries. However, the current rate of fallout can be ascribed mainly to vehicle emissions. Although many surveys and experiments comparing lead in plants and soils have been done, the contribution of root uptake to lead in crops remains uncertain. Contamination of foliage with particles of soil may be more important than uptake by roots in many instances. Foliage near motorways and other sources of airborne lead shows evidence of direct contamination, and extrapolation of the results indicates that foliar uptake accounts for most of the lead in grasses and other plants having high leaf surface area per unit mass. Translocation of lead from outer to inner leaves, and to tubers, fruits and seeds is very slight, and it seems that not more than a few μg per day of lead enters diet by this route. Measurements of the naturally-occurring radioisotope 210Pb in fallout and in diet can be used to calculate an equivalent area, defined as Equivalent area = Amount in average adult diet per day/ Amount falling per unit area of ground per day The equivalent area for 210Pb is 0.18 m 2, and if it is assumed that stable lead in fallout enters diet to the same degree as does 210Pb, it follows that together the various pathways contribute about 13 μg day -1 to the average adult diet.

  20. Coastal-ocean uptake of anthropogenic carbon

    NASA Astrophysics Data System (ADS)

    Bourgeois, Timothée; Orr, James C.; Resplandy, Laure; Terhaar, Jens; Ethé, Christian; Gehlen, Marion; Bopp, Laurent

    2016-07-01

    Anthropogenic changes in atmosphere-ocean and atmosphere-land CO2 fluxes have been quantified extensively, but few studies have addressed the connection between land and ocean. In this transition zone, the coastal ocean, spatial and temporal data coverage is inadequate to assess its global budget. Thus we use a global ocean biogeochemical model to assess the coastal ocean's global inventory of anthropogenic CO2 and its spatial variability. We used an intermediate resolution, eddying version of the NEMO-PISCES model (ORCA05), varying from 20 to 50 km horizontally, i.e. coarse enough to allow multiple century-scale simulations but finer than coarse-resolution models (˜ 200 km) to better resolve coastal bathymetry and complex coastal currents. Here we define the coastal zone as the continental shelf area, excluding the proximal zone. Evaluation of the simulated air-sea fluxes of total CO2 for 45 coastal regions gave a correlation coefficient R of 0.8 when compared to observation-based estimates. Simulated global uptake of anthropogenic carbon results averaged 2.3 Pg C yr-1 during the years 1993-2012, consistent with previous estimates. Yet only 0.1 Pg C yr-1 of that is absorbed by the global coastal ocean. That represents 4.5 % of the anthropogenic carbon uptake of the global ocean, less than the 7.5 % proportion of coastal-to-global-ocean surface areas. Coastal uptake is weakened due to a bottleneck in offshore transport, which is inadequate to reduce the mean anthropogenic carbon concentration of coastal waters to the mean level found in the open-ocean mixed layer.

  1. Sugar uptake by intestinal basolateral membrane vesicles.

    PubMed

    Wright, E M; van Os, C H; Mircheff, A K

    1980-03-27

    A high yield of membrane vesicles was prepared from the basolateral surface of rat intestinal cells using an N2 cavitation bomb and density gradient centrifugation. The membranes were enriched 10-fold and were free of significatn contamination by brush border membranes and mitochondria. The rate of D-E114C]glucose and L-E13H]glucose uptake into the vesicle was measured using a rapid filtration technique. D-Glucose equilibrated within the vesicles with a half-time 1/25th that for L-glucose. The stereospecific uptake exhibited saturation kinetics with a Km of approx. 44 mM and a V of approx. 110 nmol . mg-1 min-1 at 10 degrees C. The activation energy for the process was 14 kcal . mol-1 below 15 degrees C and it approached 3 kcal . mol-1 above 22 degrees C. Carrier-mediated uptake was eliminated in the presence of 1 mM HgCl2 and 0.5 mM phloretin. The rate of transport was unaffected by the absence or presence of sodium concentration gradients. Competition studies demonstrated that all sugars with the D-glucose pyranose ring chair conformation shared the transport system, and that, with the possible exception of the -OH group at carbon No. 1, there were no specific requirements for an equatorial -OH group at any position in the pyranose ring. In the case of alpha-methyl-D-glucoside its inability to share the D-glucose transport system may be due to steric hindrance posed by the -OCH3 group rather than by a specific requirement for a free hydroxyl group at the position in the ring. It is concluded that sugars are transported across the basolateral membrane of the intestinal epithelium by a facilitated diffusion system reminiscent of that in human red blood cells. PMID:6245688

  2. Angiotensin II reduces calcium uptake into bone.

    PubMed

    Schurman, Scott J; Bergstrom, William H; Shoemaker, Lawrence R; Welch, Thomas R

    2004-01-01

    Children with neonatal Bartter syndrome (NBS) have hypercalciuria, nephrocalcinosis, and osteopenia. A complex of basic-fibroblast growth factor (b-FGF) and a naturally occurring glycosaminoglycan has been identified in the serum and urine of NBS patients. This complex increases bone resorption in a bone disc bioassay system. Angiotensin II (AT II), which is increased in Bartter syndrome, increases the synthesis of b-FGF by cultured endothelial cells. Addition of 10(-8) M AT II to the bioassay, a concentration reported in Bartter syndrome patients, significantly decreased calcium uptake into bone discs [E/C 0.60 (0.04), P < 0.001 compared with buffer, normal E/C >0.90]. Adding b-FGF monoclonal antibody at 10 microg/ml [E/C 0.90 (0.06), P=NS] or indomethacin [E/C 1.00 (0.03), P=NS] to 10(-8 )M AT II neutralized this effect. In separate experiments, newborn rats were given intraperitoneal injections of AT II. Bone discs from these animals were used in the bioassay system and calcium uptake was markedly reduced compared with discs from rats injected with phosphate-buffered saline [AT II 6.6 x 10(-9), E/C 0.10 (0.04), P<0.001, AT II 3.3 x 10(-8), E/C 0.10 (0.05), P<0.001]. AT II decreases calcium uptake in the bone disc bioassay system. This effect can be abrogated by antibody to b-FGF or prostaglandin synthetase inhibition. These results support the hypothesis that in children with NBS, elevated levels of AT II stimulate local skeletal b-FGF synthesis, with a resultant increase in bone resorption via a prostaglandin-dependent pathway. PMID:14648327

  3. Political and economic factors influencing contraceptive uptake.

    PubMed

    Sai, F T

    1993-01-01

    International, national and local level politics influence the uptake of contraception through consensuses, laws, financial and moral support or the creation of an enabling atmosphere. Opposition to contraception generally comes from some churches and groups opposed to particular technologies. Socio-economic factors, particularly education, the health care system and the perceived or actual cost of fertility regulation as compared to benefits expected from children also powerfully influence contraceptive use. For many poor women in developing countries their powerlessness in relation to their male partners is an important obstacle. PMID:8324609

  4. Plant Nitrogen Uptake in Terrestrial Biogeochemical Models

    NASA Astrophysics Data System (ADS)

    Marti Donati, A.; Cox, P.; Smith, M. J.; Purves, D.; Sitch, S.; Jones, C. D.

    2013-12-01

    higher atmospheric CO2 concentrations than originally expected. This study compares the differences in the predictions of alternative models of plant N uptake found in different terrestrial biogeochemical models with the predictions from a new N-uptake model developed under the Joint UK Land Environment Simulator (JULES) framework. We implement a methodology for the construction, parameterization and evaluation of N uptake models to fully decompose all the N uptake component processes in terms of their parameter uncertainty and the accuracy of their predictions with respect to different empirical data sets. Acknowledgements This work has been funded by the European Commission FP7-PEOPLE-ITN-2008 Marie Curie Action: "Greencycles II: FP7-PEOPLE-ITN-2008 Marie Curie Action: "Networks for Initial Training"

  5. Effects of methysergide on platelets incubated with reserpine

    PubMed Central

    Cumings, J. N.; Hilton, Barbara P.

    1971-01-01

    1. Platelets were incubated with methysergide and related compounds (2-bromo lysergic acid (BOL), ergotamine and methyl ergotamine) together with reserpine. 2. Methysergide inhibited the normal aggregation response of platelets to 5-hydroxytryptamine (5HT) but did not affect the reduction in the 5HT content caused by reserpine, or the uptake of 5HT by the platelets. 3. BOL, ergotamine and methyl ergotamine behaved similarly. Methysergide had greater anti5HT potency than BOL, and methyl ergotamine had greater potency than ergotamine. 4. The use of platelets as a model for synaptic preparations is discussed. 5. The role of 5HT receptor sites on the platelet membrane and the significance of the results for migraine patients treated with methysergide are discussed. PMID:5116036

  6. Similarity in microbial amino acid uptake in surface waters of the North and South Atlantic (sub-)tropical gyres

    NASA Astrophysics Data System (ADS)

    Hill, Polly G.; Mary, Isabelle; Purdie, Duncan A.; Zubkov, Mikhail V.

    2011-12-01

    The Earth’s most extensive biomes - the oceanic subtropical gyres - are considered to be expanding with current surface ocean warming. Although it is well established that microbial communities control gyre biogeochemistry, comparisons of their metabolic activities between gyres are limited. In order to estimate metabolic activities including production of microbial communities, the uptake rates of amino acids leucine, methionine and tyrosine at ambient concentrations were estimated in surface waters of the Atlantic Ocean using radioisotopically labelled tracers. Data were acquired during six research cruises covering main oceanic provinces herein termed: North and South Atlantic Gyres, Bermuda Atlantic Time-series Study site (BATS), Equatorial region, and Mauritanian Upwelling (off Cape Blanc). Data were divided between provinces, the extents of which were identified by ocean colour data, in order to achieve provincial mean uptake rates. Leucine and methionine uptake rates did not differ between sampling periods, and were comparable between the North and South subtropical gyres. Furthermore, variation in uptake rates measured throughout the two oligotrophic gyres, where sampling covered ∼4 × 10 6 km 2, was considerably lower than that measured within the Mauritanian Upwelling and Equatorial regions, and even at the BATS site. Tyrosine was generally the slowest of the amino acids to be taken up, however, it was assimilated faster than methionine within the Mauritanian Upwelling region. Thus, we propose that one value for leucine (12.6 ± 3.2 pmol L -1 h -1) and methionine (10.0 ± 3.3 pmol L -1 h -1) uptake could be applied to the oligotrophic subtropical gyres of the Atlantic Ocean. However, with the significantly lower uptake rates observed at the BATS site, we would not advise extrapolation to the Sargasso Sea.

  7. Assessment of producers' response to Salmonella biosecurity issues and uptake of advice on laying hen farms in England and Wales.

    PubMed

    Gosling, R J; Martelli, F; Wintrip, A; Sayers, A R; Wheeler, K; Davies, R H

    2014-01-01

    High standards of biosecurity are known to reduce the risk of disease outbreaks; however, uptake of advice and implementation of biosecurity measures are dependent on many factors. This study assessed the uptake of targeted biosecurity advice by 60 laying hen farms provided during biosecurity audit visits. Advice was provided as bullet point cards focusing on specific areas identified as benefitting from improvement. These covered site entrance, site tidiness, vaccination, boot hygiene, hand hygiene, house tidiness, rodent control, fly control, red mite control and cleaning and disinfection between flocks. Background knowledge of Salmonella and biosecurity and farmers' willingness and intent to implement additional measures were assessed. About 50% of the principal decision-makers had basic background knowledge of Salmonella, with 22% considered well informed; almost all agreed that biosecurity could impact on Salmonella control and many appeared willing to implement additional biosecurity measures. Sixty-three per cent of study farms were categorised using the Defra Farmer Segmentation Model as Modern Family Businesses (MFBs), with 7-11% of farms being categorised as Custodian, Lifestyle Choice, Pragmatist or Challenged Enterprise; however, categorisation, did not determine uptake of advice. The most frequently used advice cards were boot hygiene, red mite control, hand hygiene, site entrance and cleaning and disinfection; uptake of advice ranged from 54 to 80% depending on the advice card. Uptake of advice by the farmers was encouraging, especially considering it was being provided by people other than their usual source of biosecurity information. Those who did not implement the recommended measures cited cost, difficulty of enforcement and practicality as the main reasons. However, the positive uptake of advice and implementation of recommended measures by many farmers demonstrates that targeted advice, discussed face to face with farmers, on a small number of

  8. Patterns of radioiodine uptake by the lactating breast.

    PubMed

    Bakheet, S M; Hammami, M M

    1994-07-01

    Breast uptake of radioiodine, if not suspected, may be misinterpreted as thyroid cancer metastasis to the lung. To characterize the patterns of radioiodine breast uptake, we retrospectively studied 20 radioiodine scans that were performed within 1 week of cessation of breast feeding. Four patterns of uptake were identified: "full", "focal", "crescent" and "irregular". The uptake was asymmetric in 60% (left > right in 45%, right > left in 15%), symmetric in 25% and unilateral in 15% of cases. A characteristic full bilateral uptake was present in 40% of cases. In three cases with the irregular pattern, caused in part by external contamination with radioactive milk, the uptake closely mimicked lung metastases. Delayed images, obtained in one case, showed an apparent radioiodine shift from the breast to the thyroid, suggesting that the presence of breast uptake can modulate radioiodine uptake by thyroid tissue. In a case of unilateral breast uptake, a history of mastitis was obtained, which to our knowledge has not been previously reported. Breast uptake of radioiodine may take several scintigraphic patterns that are not always characteristic of the lactating breast and may affect the apparent extent of thyroid remnant/metastasis. PMID:7957345

  9. Cyclic variations in nitrogen uptake rate in soybean plants: uptake during reproductive growth

    NASA Technical Reports Server (NTRS)

    Vessey, J. K.; Raper, C. D. Jr; Henry, L. T.; Raper CD, J. r. (Principal Investigator)

    1990-01-01

    Net uptake of NO3- by non-nodulated soybean plants [Glycine max (L.) Merr. cv. Ransom] growing in flowing hydroponic culture was measured daily during a 63 d period of reproductive development between the first florally inductive photoperiod and [unknown word] seed growth. Removal of NO3- from a replenished solution containing 1.0 mol m-3 NO3- was determined by ion chromatography. Uptake of NO3- continued throughout reproductive development. The net uptake rate of NO3- cycled between maxima and minima with a periodicity of oscillation of 3 to 7 d during the floral stage and about 6 d during the fruiting stage. Coupled with increasing concentrations of carbon and C : N ratios in tissues, the oscillations in net uptake rates of NO3- are evidence that the demand for carbohydrate by reproductive organs is contingent on the availability of nitrogen in the shoot pool rather than that the demand for nitrogen follows the flux of carbohydrate into reproductive tissues.

  10. Quantitative fluorescence imaging reveals point of release for lipoproteins during LDLR-dependent uptake[S

    PubMed Central

    Pompey, Shanica; Zhao, Zhenze; Luby-Phelps, Kate; Michaely, Peter

    2013-01-01

    The LDL receptor (LDLR) supports efficient uptake of both LDL and VLDL remnants by binding lipoprotein at the cell surface, internalizing lipoprotein through coated pits, and releasing lipoprotein in endocytic compartments before returning to the surface for further rounds of uptake. While many aspects of lipoprotein binding and receptor entry are well understood, it is less clear where, when, and how the LDLR releases lipoprotein. To address these questions, the current study employed quantitative fluorescence imaging to visualize the uptake and endosomal processing of LDL and the VLDL remnant β-VLDL. We find that lipoprotein release is rapid, with most release occurring prior to entry of lipoprotein into early endosomes. Published biochemical studies have identified two mechanisms of lipoprotein release: one that involves the β-propeller module of the LDLR and a second that is independent of this module. Quantitative imaging comparing uptake supported by the normal LDLR or by an LDLR variant incapable of β-propeller-dependent release shows that the β-propeller-independent process is sufficient for release for both lipoproteins but that the β-propeller process accelerates both LDL and β-VLDL release. Together these findings define where, when, and how lipoprotein release occurs and provide a generalizable methodology for visualizing endocytic handling in situ. PMID:23296879

  11. Freehand SPECT in low uptake situations

    NASA Astrophysics Data System (ADS)

    Lasser, Tobias; Ziegler, Sibylle I.; Navab, Nassir

    2011-03-01

    3D functional imaging in the operating room can be extremely useful for some procedures like SLN mapping or SLN biopsies. Freehand SPECT is an example of such an imaging modality, combining manually scanned, hand-held 1D gamma detectors with spatial positioning systems in order to reconstruct localized 3D SPECT images, for example in the breast or neck region. Standard series expansion methods are applied together with custom physical models of the acquisition process and custom filtering procedures to perform 3D tomographic reconstruction from sparse, limited-angle and irregularly sampled data. A Freehand SPECT system can easily be assembled on a mobile cart suitable for use in the operating room. This work addresses in particular the problem of objects with low uptake (like sentinel lymph nodes), where reconstruction tends to be difficult due to low signal to noise ratio. In a neck-like phantom study, we show that four simulated nodes of 250 microliter volume with 0.06% respectively 0.03% uptake of a virtual 70MBq injection of Tc99m (the typical activity for SLN procedures at our hospital) in a background of water can be reconstructed successfully using careful filtering procedures in the reconstruction pipeline. Ten independent Freehand SPECT scans of the phantom were performed by several different operators, with an average scan duration of 5.1 minutes. The resulting reconstructions show an average spatial accuracy within voxel dimensions (2.5mm) compared to CT and exhibit correct relative quantification.

  12. Mitochondrial calcium uptake capacity modulates neocortical excitability

    PubMed Central

    Sanganahalli, Basavaraju G; Herman, Peter; Hyder, Fahmeed; Kannurpatti, Sridhar S

    2013-01-01

    Local calcium (Ca2+) changes regulate central nervous system metabolism and communication integrated by subcellular processes including mitochondrial Ca2+ uptake. Mitochondria take up Ca2+ through the calcium uniporter (mCU) aided by cytoplasmic microdomains of high Ca2+. Known only in vitro, the in vivo impact of mCU activity may reveal Ca2+-mediated roles of mitochondria in brain signaling and metabolism. From in vitro studies of mitochondrial Ca2+ sequestration and cycling in various cell types of the central nervous system, we evaluated ranges of spontaneous and activity-induced Ca2+ distributions in multiple subcellular compartments in vivo. We hypothesized that inhibiting (or enhancing) mCU activity would attenuate (or augment) cortical neuronal activity as well as activity-induced hemodynamic responses in an overall cytoplasmic and mitochondrial Ca2+-dependent manner. Spontaneous and sensory-evoked cortical activities were measured by extracellular electrophysiology complemented with dynamic mapping of blood oxygen level dependence and cerebral blood flow. Calcium uniporter activity was inhibited and enhanced pharmacologically, and its impact on the multimodal measures were analyzed in an integrated manner. Ru360, an mCU inhibitor, reduced all stimulus-evoked responses, whereas Kaempferol, an mCU enhancer, augmented all evoked responses. Collectively, the results confirm aforementioned hypotheses and support the Ca2+ uptake-mediated integrative role of in vivo mitochondria on neocortical activity. PMID:23591650

  13. Imaging neurotransmitter uptake and depletion in astrocytes

    SciTech Connect

    Tan, W. |; Haydon, P.G.; Yeung, E.S.

    1997-08-01

    An ultraviolet (UV) laser-based optical microscope and charge-coupled device (CCD) detection system was used to obtain chemical images of biological cells. Subcellular structures can be easily seen in both optical and fluorescence images. Laser-induced native fluorescence detection provides high sensitivity and low limits of detection, and it does not require coupling to fluorescent dyes. We were able to quantitatively monitor serotonin that has been taken up into and released from individual astrocytes on the basis of its native fluorescence. Different regions of the cells took up different amounts of serotonin with a variety of uptake kinetics. Similarly, we observed different serotonin depletion dynamics in different astrocyte regions. There were also some astrocyte areas where no serotonin uptake or depletion was observed. Potential applications include the mapping of other biogenic species in cells as well as the ability to image their release from specific regions of cells in response to external stimuli. {copyright} {ital 1997} {ital Society for Applied Spectroscopy}

  14. Abiotic uptake of gases by organic soils

    NASA Astrophysics Data System (ADS)

    Smagin, A. V.

    2007-12-01

    Methodological and experimental studies of the abiotic uptake of gaseous substances by organic soils were performed. The static adsorption method of closed vessels for assessing the interaction of gases with the solid and liquid soil phases and the dynamic method of determining the sorption isotherms of gases by soils were analyzed. The theoretical substantiation of the methods and their practical implementations on the basis of a PGA-7 portable gas analyzer (Russia) were considered. Good agreement between the equilibrium sorption isotherms of the gases and the Langmuir model was revealed; for the real ranges of natural gas concentrations, this model can be reduced to the linear Henry equation. The limit values of the gas sorption (Langmuir monolayer capacity) are typical for dry samples; they vary from 670 4000 g/m3 for methane and oxygen to 20 000 25 000 g/m3 for carbon dioxide. The linear distribution coefficients of gases between the solid and gas phases of organic soils (Henry constants) are 8 18 units for poorly sorbed gases (O2, CH4) and 40 60 units for CO2. The kinetics of the chemicophysical uptake of gases by the soil studied is linear in character and obeys the relaxation kinetic model of the first order with the corresponding relaxation constants, which vary from 1 h -1 in wet samples to 10 h -1 in dry samples.

  15. Iron uptake and transport across physiological barriers.

    PubMed

    Duck, Kari A; Connor, James R

    2016-08-01

    Iron is an essential element for human development. It is a major requirement for cellular processes such as oxygen transport, energy metabolism, neurotransmitter synthesis, and myelin synthesis. Despite its crucial role in these processes, iron in the ferric form can also produce toxic reactive oxygen species. The duality of iron's function highlights the importance of maintaining a strict balance of iron levels in the body. As a result, organisms have developed elegant mechanisms of iron uptake, transport, and storage. This review will focus on the mechanisms that have evolved at physiological barriers, such as the intestine, the placenta, and the blood-brain barrier (BBB), where iron must be transported. Much has been written about the processes for iron transport across the intestine and the placenta, but less is known about iron transport mechanisms at the BBB. In this review, we compare the established pathways at the intestine and the placenta as well as describe what is currently known about iron transport at the BBB and how brain iron uptake correlates with processes at these other physiological barriers. PMID:27457588

  16. Microbiology and Moisture Uptake of Desert Soils

    NASA Astrophysics Data System (ADS)

    Kress, M. E.; Bryant, E. P.; Morgan, S. W.; Rech, S.; McKay, C. P.

    2005-12-01

    We have initiated an interdisciplinary study of the microbiology and water content of desert soils to better understand microbial activity in extreme arid environments. Water is the one constituent that no organism can live without; nevertheless, there are places on Earth with an annual rainfall near zero that do support microbial ecosystems. These hyperarid deserts (e.g. Atacama and the Antarctic Dry Valleys) are the closest terrestrial analogs to Mars, which is the subject of future exploration motivated by the search for life beyond Earth. We are modeling the moisture uptake by soils in hyperarid environments to quantify the environmental constraints that regulate the survival and growth of micro-organisms. Together with the studies of moisture uptake, we are also characterizing the microbial population in these soils using molecular and culturing methods. We are in the process of extracting DNA from these soils using MoBio extraction kits. This DNA will be used as a template to amplify bacterial and eukaryotic ribosomal DNA to determine the diversity of the microbial population. We also have been attempting to determine the density of organisms by culturing on one-half strength R2A agar. The long-range goal of this research is to identify special adaptations of terrestrial life that allow them to inhabit extreme arid environments, while simultaneously quantifying the environmental parameters that enforce limits on these organisms' growth and survival.

  17. Vaccine production, distribution, access, and uptake.

    PubMed

    Smith, Jon; Lipsitch, Marc; Almond, Jeffrey W

    2011-07-30

    For human vaccines to be available on a global scale, complex production methods, meticulous quality control, and reliable distribution channels are needed to ensure that the products are potent and effective at the point of use. The technologies used to manufacture different types of vaccines can strongly affect vaccine cost, ease of industrial scale-up, stability, and, ultimately, worldwide availability. The complexity of manufacturing is compounded by the need for different formulations in different countries and age-groups. Reliable vaccine production in appropriate quantities and at affordable prices is the cornerstone of developing global vaccination policies. However, to ensure optimum access and uptake, strong partnerships are needed between private manufacturers, regulatory authorities, and national and international public health services. For vaccines whose supply is insufficient to meet demand, prioritisation of target groups can increase the effect of these vaccines. In this report, we draw from our experience of vaccine development and focus on influenza vaccines as an example to consider production, distribution, access, and other factors that affect vaccine uptake and population-level effectiveness. PMID:21664680

  18. Gallium-68 PSMA uptake in adrenal adenoma.

    PubMed

    Law, W Phillip; Fiumara, Frank; Fong, William; Miles, Kenneth A

    2016-08-01

    Gallium-68 (Ga-68) labelled prostate-specific membrane antigen (PSMA) imaging by positron emission tomography (PET) has emerged as a promising tool for staging of prostate cancer and restaging of disease in recurrence or biochemical failure after definitive treatment of prostate cancer. Ga-68 PSMA PET produces high target-to-background images of prostate cancer and its metastases which are reflective of the significant overexpression of PSMA in these cells and greatly facilitates tumour detection. However, relatively little is known about the PSMA expression of benign neoplasms and non-prostate epithelial malignancies. This is a case report of PSMA uptake in an adrenal adenoma incidentally discovered on PET performed for restaging of biochemically suspected prostate cancer recurrence. With the increasing use of PSMA PET in the management of prostate cancer - and the not infrequent occurrence of adrenal adenomas - the appearance of low- to moderate-grade PSMA uptake in adrenal adenomas should be one with which reporting clinicians are familiar. PMID:26394552

  19. Uptake and partitioning of zinc in Lemnaceae.

    PubMed

    Lahive, Elma; O'Callaghan, Michael J A; Jansen, Marcel A K; O'Halloran, John

    2011-11-01

    Macrophytes provide food and shelter for aquatic invertebrates and fish, while also acting as reservoirs for nutrients and trace elements. Zinc accumulation has been reported for various Lemnaceae species. However, comparative accumulation across species and the link between zinc accumulation and toxicity are poorly understood. Morphological distribution and cellular storage, in either bound or soluble form, are important for zinc tolerance. This study shows differences in the uptake and accumulation of zinc by three duckweed species. Landoltia punctata and Lemna minor generally accumulated more zinc than Lemna gibba. L. minor, but not L. gibba or L. punctata, accumulated greater concentrations of zinc in roots compared to fronds when exposed to high levels of zinc. The proportion of zinc stored in the bound form relative to the soluble-form was higher in L. minor. L. punctata accumulated greater concentrations of zinc in fronds compared to roots and increased the proportion of zinc it stored in the soluble form, when exposed to high zinc levels. L. gibba is the only species that significantly accumulated zinc at low concentrations, and was zinc-sensitive. Overall, internal zinc concentrations showed no consistent correlation with toxic effect. We conclude that relationships between zinc toxicity and uptake and accumulation are species specific reflecting, among others, zinc distribution and storage. Differences in zinc distribution and storage are also likely to have implications for zinc bioavailability and trophic mobility. PMID:21755349

  20. Iodide uptake by negatively charged clay interlayers?

    PubMed

    Miller, Andrew; Kruichak, Jessica; Mills, Melissa; Wang, Yifeng

    2015-09-01

    Understanding iodide interactions with clay minerals is critical to quantifying risk associated with nuclear waste disposal. Current thought assumes that iodide does not interact directly with clay minerals due to electrical repulsion between the iodide and the negatively charged clay layers. However, a growing body of work indicates a weak interaction between iodide and clays. The goal of this contribution is to report a conceptual model for iodide interaction with clays by considering clay mineral structures and emergent behaviors of chemical species in confined spaces. To approach the problem, a suite of clay minerals was used with varying degrees of isomorphic substitution, chemical composition, and mineral structure. Iodide uptake experiments were completed with each of these minerals in a range of swamping electrolyte identities (NaCl, NaBr, KCl) and concentrations. Iodide uptake behaviors form distinct trends with cation exchange capacity and mineral structure. These trends change substantially with electrolyte composition and concentration, but do not appear to be affected by solution pH. The experimental results suggest that iodide may directly interact with clays by forming ion-pairs (e.g., NaI(aq)) which may concentrate within the interlayer space as well as the thin areas surrounding the clay particle where water behavior is more structured relative to bulk water. Ion pairing and iodide concentration in these zones is probably driven by the reduced dielectric constant of water in confined space and by the relatively high polarizability of the iodide species. PMID:26057987

  1. Promoting screening mammography: insight or uptake?

    PubMed

    Keen, John D

    2010-01-01

    The US Preventive Services Task Force has emphasized individualized decision-making regarding participation in screening mammography for women ages 40 to 49. Positive public opinion regarding screening mammography is understandable given that screening advocates have heavily promoted the slogan "early detection saves lives" while ignoring screening harms. The goal of mammography screening advocates is to increase screening participation or uptake. The purpose of this paper is to promote physician and patient insight by presenting the age-related benefit and harms of screening. At age 50, routine screening saves approximately 1 woman per 1000 over 10 years. The life-saving proportion of screen-detected cancers is 5%, which means mammograms must detect 21 cancers to save one life. Almost half of screen-detected cancers represent pseudo-disease and would never become symptomatic yet alone lethal during a woman's lifetime. Consequently, 40- and 50-year-old women are 10 times more likely to experience overdiagnosis and overtreatment than to have their lives saved. Analysis of events and outcomes per single screening round for women ages 40 to 49 show that approximately 9600 screening mammograms, 960 diagnostic exams, and 90 to 140 biopsies are required to save one life. Given the substantial harms of screening, advocates should refocus their priority from promoting uptake to promoting insight. PMID:21057074

  2. Pathways of Arsenic Uptake and Efflux

    PubMed Central

    Yang, Hung-Chi; Fu, Hsueh-Liang; Lin, Yung-Feng; Rosen, Barry P.

    2015-01-01

    Arsenic is the most prevalent environmental toxic substance and ranks first on the U.S. Environmental Protection Agency’s Superfund List. Arsenic is a carcinogen and a causative agent of numerous human diseases. Paradoxically arsenic is used as a chemotherapeutic agent for treatment of acute promyelocytic leukemia. Inorganic arsenic has two biological important oxidation states: As(V) (arsenate) and As(III) (arsenite). Arsenic uptake is adventitious because the arsenate and arsenite are chemically similar to required nutrients. Arsenate resembles phosphate and is a competitive inhibitor of many phosphate-utilizing enzymes. Arsenate is taken up by phosphate transport systems. In contrast, at physiological pH, the form of arsenite is As(OH)3, which resembles organic molecules such as glycerol. Consequently, arsenite is taken into cells by aquaglyceroporin channels. Arsenic efflux systems are found in nearly every organism and evolved to rid cells of this toxic metalloid. These efflux systems include members of the multidrug resistance protein family and the bacterial exchangers Acr3 and ArsB. ArsB can also be a subunit of the ArsAB As(III)-translocating ATPase, an ATP-driven efflux pump. The ArsD metallochaperone binds cytosolic As(III) and transfers it to the ArsA subunit of the efflux pump. Knowledge of the pathways and transporters for arsenic uptake and efflux is essential for understanding its toxicity and carcinogenicity and for rational design of cancer chemotherapeutic drugs. PMID:23046656

  3. Update on cerebral uptake of blood ammonia.

    PubMed

    Sørensen, Michael

    2013-06-01

    Ammonia is believed to play a key role in the development of hepatic encephalopathy (HE) with increased formation of glutamine playing a central role. It has been debated whether blood ammonia enters the brain by passive diffusion and/or active transport by ion-transporters and that changes in blood pH could affect the blood-to-brain transfer of ammonia. It has also been proposed that the permeability-surface area product for ammonia across the blood-brain barrier (PSBBB) should be increased in cirrhosis and HE. In the present paper it is argued that changes in blood pH does not alter PSBBB for ammonia and the question of passive diffusion versus active transport of ammonia remains unresolved. Furthermore, recent studies do not find evidence for increased PSBBB for ammonia in cirrhosis. The main determent for cerebral uptake of blood ammonia (i.e. flux) is the arterial blood ammonia concentration. This means that the only way to protect the brain from hyperammonemia is by lowering blood ammonia, inhibit cerebral uptake of ammonia, or by manipulating cerebral ammonia metabolism so that less glutamine is produced. PMID:23479402

  4. A porous metal-organic framework with ultrahigh acetylene uptake capacity under ambient conditions.

    PubMed

    Pang, Jiandong; Jiang, Feilong; Wu, Mingyan; Liu, Caiping; Su, Kongzhao; Lu, Weigang; Yuan, Daqiang; Hong, Maochun

    2015-01-01

    Acetylene, an important petrochemical raw material, is very difficult to store safely under compression because of its highly explosive nature. Here we present a porous metal-organic framework named FJI-H8, with both suitable pore space and rich open metal sites, for efficient storage of acetylene under ambient conditions. Compared with existing reports, FJI-H8 shows a record-high gravimetric acetylene uptake of 224 cm(3) (STP) g(-1) and the second-highest volumetric uptake of 196 cm(3) (STP) cm(-3) at 295 K and 1 atm. Increasing the storage temperature to 308 K has only a small effect on its acetylene storage capacity (∼200 cm(3) (STP) g(-1)). Furthermore, FJI-H8 exhibits an excellent repeatability with only 3.8% loss of its acetylene storage capacity after five cycles of adsorption-desorption tests. Grand canonical Monte Carlo simulation reveals that not only open metal sites but also the suitable pore space and geometry play key roles in its remarkable acetylene uptake. PMID:26123775

  5. A porous metal-organic framework with ultrahigh acetylene uptake capacity under ambient conditions

    PubMed Central

    Pang, Jiandong; Jiang, Feilong; Wu, Mingyan; Liu, Caiping; Su, Kongzhao; Lu, Weigang; Yuan, Daqiang; Hong, Maochun

    2015-01-01

    Acetylene, an important petrochemical raw material, is very difficult to store safely under compression because of its highly explosive nature. Here we present a porous metal-organic framework named FJI-H8, with both suitable pore space and rich open metal sites, for efficient storage of acetylene under ambient conditions. Compared with existing reports, FJI-H8 shows a record-high gravimetric acetylene uptake of 224 cm3 (STP) g−1 and the second-highest volumetric uptake of 196 cm3 (STP) cm−3 at 295 K and 1 atm. Increasing the storage temperature to 308 K has only a small effect on its acetylene storage capacity (∼200 cm3 (STP) g−1). Furthermore, FJI-H8 exhibits an excellent repeatability with only 3.8% loss of its acetylene storage capacity after five cycles of adsorption–desorption tests. Grand canonical Monte Carlo simulation reveals that not only open metal sites but also the suitable pore space and geometry play key roles in its remarkable acetylene uptake. PMID:26123775

  6. Elemental uptake and distribution of nutrients in avocado mesocarp and the impact of soil quality.

    PubMed

    Reddy, Mageshni; Moodley, Roshila; Jonnalagadda, Sreekanth B

    2014-07-01

    The distribution of 14 elements (both essential and non-essential) in the Hass and Fuerte cultivars of avocados grown at six different sites in KwaZulu-Natal, South Africa, was investigated. Soils from the different sites were concurrently analysed for elemental concentration (both total and exchangeable), pH, organic matter and cation exchange capacity. In both varieties of the fruit, concentrations of the elements Cd, Co, Cr, Pb and Se were extremely low with the other elements being in decreasing order of Mg > Ca > Fe > Al > Zn > Mn > Cu > Ni > As. Nutritionally, avocados were found to be a good dietary source of the micronutrients Cu and Mn. In soil, Pb concentrations indicated enrichment (positive geoaccumuluation indices) but this did not influence uptake of the metal by the plant. Statistical analysis was done to evaluate the impact of soil quality parameters on the nutrient composition of the fruits. This analysis indicated the prevalence of complex metal interactions at the soil-plant interface that influenced their uptake by the plant. However, the plant invariably controlled metal uptake according to metabolic needs as evidenced by their accumulation and exclusion. PMID:24671616

  7. A hierarchical examination of methane uptake: field patterns, lab physiology, community composition and biogeography

    NASA Astrophysics Data System (ADS)

    von Fischer, J. C.; Koyama, A.; Johnson, N. G.; Webb, C. T.

    2015-12-01

    Scaling problems abound in biogeochemistry. At the finest scale, soil microbes experience habitats and environmental changes that affect the chemical transformations of interest. We collect the DNA of these organisms from sites across landscapes and note differences in who is there, and we seek to evaluate why group membership changes in space (biogeography) and why activity rates change over time (physiology). The goal of efforts at finer scales is often to better predict patterns at larger scales. We conducted such a hierarchical examination of methane uptake in the Great Plains grasslands of North America, gathering data from 22 plots at 8 field locations, scattered from South Dakota to New Mexico and Colorado to Kansas. Our work provides insight into methanotroph biogeochemistry at all of these scales. For example, we found that methane uptake rates vary mostly due to the methanotroph activity, and less so due to diffusivity. A combination of field and lab observations reveal that methanotroph communities differ in their sensitivity to soil moisture and to ammonium (an inhibitor of methanotrophy). Examination of methanotroph community composition reveals tantalizing patterns in composition, dominance and richness across sites, that appears to be structured by patterns of precipitation and soil texture. We anticipate that greater synthesis of these hierarchical findings will paint a richer picture of methanotroph life and enable improved prediction of methane uptake at regional scales.

  8. Can Canopy Uptake Influence Nitrogen Acquisition and Allocation by Trees?

    NASA Astrophysics Data System (ADS)

    Nair, Richard; Perks, Mike; Mencuccini, Maurizio

    2015-04-01

    Nitrogen (N) fertilization due to atmospheric deposition of anthropogenic nitrogen (NDEP) may explain some of the net carbon (C) sink (0.6-0.7 Pg y-1) in temperate forests, but estimates of the additional C uptake due to atmospheric N additions (ΔCΔN) can vary by over an order of magnitude (~ 5 to 200 ΔCΔN). High estimates from several recent studies [e.g. Magnani (2007), Nature 447 848-850], deriving ΔCΔN from regional correlations between NDEP and measures of C uptake (such as eddy covariance -derived net ecosystem production, or forest inventory data) contradict estimates from other studies of 15N tracer applications added as fertilizer to the forest floor. A strong ΔCΔN effect requires nitrogen to be efficiently acquired by trees and allocated to high C:N, long-lived woody tissues, but these isotope experiments typically report relatively little (~ 20 %) of 15N added is found above-ground, with < 5 % of the total 15N applied found in wood. Consequently the high correlation-derived ΔCΔN estimates are often attributed to co-variation with other factors across the range of sites investigated. However 15N-fertilization treatments often impose considerably higher total N loads than ambient NDEP and almost exclusively only apply mineral 15N treatments to the soil, often in a limited number of treatment events over relatively short periods of time. Excessive N deposition loads can induce negative physiological effects and limit the resulting ΔCΔN observed, and applying treatments to the soil may ignore the importance of canopy nitrogen uptake in overall forest nutrition. As canopies can directly take up nitrogen, the chronic, (relatively) low levels of ambient NDEP inputs from pollution may be acquired without some of the effects of heavy N loads, obtaining this N before it reaches the soil, and allowing canopies to substitute for, or supplement, edaphic N nutrition. The strength of this effect depends on how much N uptake can occur across the canopy under

  9. Attempt at ESR dating of tooth enamel of French middle Pleistocene sites.

    PubMed

    Bahain, J J; Sarcia, M N; Falguères, C; Yokoyama, Y

    1993-01-01

    Tooth enamel samples from four important French middle Pleistocene sites are analyzed by the ESR method. ESR ages were calculated using uranium uptake mathematical models and compared with U-series results. PMID:8386043

  10. Estimation of stream nutrient uptake from nutrient addition experiments

    SciTech Connect

    Payn, Robert

    2005-09-01

    Nutrient uptake in streams is often quantified by determining nutrient uptake length. However, current methods for measuring nutrient uptake length are often impractical, expensive, or demonstrably incorrect. We have developed a new method to estimate ambient nutrient uptake lengths using field experiments involving several levels of nutrient addition. Data analysis involves plotting nutrient addition uptake lengths versus added concentration and extrapolating to the negative ambient concentration. This method is relatively easy, inexpensive, and based on sound theoretical development. It is more accurate than the commonly used method involving a single nutrient addition. The utility of the method is supported by field studies directly comparing our new method with isotopic tracer methods for determining uptake lengths of phosphorus, ammonium, and nitrate. Our method also provides parameters for comparing potential nutrient limitation among streams.

  11. Uptake of acetylene on cosmic dust and production of benzene in Titan's atmosphere

    NASA Astrophysics Data System (ADS)

    Frankland, Victoria L.; James, Alexander D.; Sánchez, Juan Diego Carrillo; Mangan, Thomas P.; Willacy, Karen; Poppe, Andrew R.; Plane, John M. C.

    2016-11-01

    A low-temperature flow tube and ultra-high vacuum apparatus were used to explore the uptake and heterogeneous chemistry of acetylene (C2H2) on cosmic dust analogues over the temperature range encountered in Titan's atmosphere below 600 km. The uptake coefficient, γ, was measured at 181 K to be (1.6 ± 0.4) × 10-4, (1.9 ± 0.4) × 10-4 and (1.5 ± 0.4) × 10-4 for the uptake of C2H2 on Mg2SiO4, MgFeSiO4 and Fe2SiO4, respectively, indicating that γ is independent of Mg or Fe active sites. The uptake of C2H2 was also measured on SiO2 and SiC as analogues for meteoric smoke particles in Titan's atmosphere, but was found to be below the detection limit (γ < 6 × 10-8 and < 4 × 10-7, respectively). The rate of cyclo-trimerization of C2H2 to C6H6 was found to be 2.6 × 10-5 exp(-741/T) s-1, with an uncertainty ranging from ± 27 % at 115 K to ± 49 % at 181 K. A chemical ablation model was used to show that the bulk of cosmic dust particles (radius 0.02-10 μm) entering Titan's atmosphere do not ablate (< 1% mass loss through sputtering), thereby providing a significant surface for heterogeneous chemistry. A 1D model of dust sedimentation shows that the production of C6H6via uptake of C2H2 on cosmic dust, followed by cyclo-trimerization and desorption, is probably competitive with gas-phase production of C6H6 between 80 and 120 km.

  12. The Gas6-Axl Protein Interaction Mediates Endothelial Uptake of Platelet Microparticles.

    PubMed

    Happonen, Kaisa E; Tran, Sinh; Mörgelin, Matthias; Prince, Raja; Calzavarini, Sara; Angelillo-Scherrer, Anne; Dahlbäck, Björn

    2016-05-13

    Upon activation, platelets release plasma membrane-derived microparticles (PMPs) exposing phosphatidylserine on their surface. The functions and clearance mechanism of these microparticles are incompletely understood. As they are pro-coagulant and potentially pro-inflammatory, rapid clearance from the circulation is essential for prevention of thrombotic diseases. The tyrosine kinase receptors Tyro3, Axl, and Mer (TAMs) and their ligands protein S and Gas6 are involved in the uptake of phosphatidylserine-exposing apoptotic cells in macrophages and dendritic cells. Both TAMs and their ligands are expressed in the vasculature, the functional significance of which is poorly understood. In this study, we investigated how vascular TAMs and their ligands may mediate endothelial uptake of PMPs. PMPs, generated from purified human platelets, were isolated by ultracentrifugation and labeled with biotin or PKH67. The uptake of labeled microparticles in the presence of protein S and Gas6 in human aortic endothelial cells and human umbilical vein endothelial cells was monitored by flow cytometry, Western blotting, and confocal/electron microscopy. We found that both endothelial cell types can phagocytose PMPs, and by using TAM-blocking antibodies or siRNA knockdown of individual TAMs, we show that the uptake is mediated by endothelial Axl and Gas6. As circulating PMP levels were not altered in Gas6(-/-) mice compared with Gas6(+/+) mice, we hypothesize that the Gas6-mediated uptake is not a means to clear the bulk of circulating PMPs but may serve to locally phagocytose PMPs generated at sites of platelet activation and as a way to effect endothelial responses. PMID:27006397

  13. RAI Thyroid Bed Uptake After Total Thyroidectomy: A Novel SPECT-CT Anatomic Classification System

    PubMed Central

    Zeuren, Rebecca; Biagini, Agnese; Grewal, Ravinder K.; Randolph, Gregory W.; Kamani, Dipti; Sabra, Mona M.; Shaha, Ashok R.; Tuttle, R. Michael

    2016-01-01

    Objective Recent, more selective use of radioactive iodine (RAI) has led to reevaluation of the clinical importance of achieving complete total thyroidectomy with minimal residual normal thyroid tissue. We utilize the improved localization by post-RAI remnant ablation, single photon emission computerized tomography-computed tomography (SPECT-CT) to define specific anatomic sites of residual RAI-uptake foci after total thyroidectomy for differentiated thyroid cancer (DTC) and to provide a novel classification system relating uptake to thyroid anatomy and preservation of adjacent neural structures. Study Design Retrospective. Method Radioactive iodine-uptake foci in thyroid bed were localized by SPECT/CT imaging at the time of RAI remnant ablation in 141 DTC patients undergoing total thyroidectomy. Results Minimal residual RAI uptake (median 0.32% at 24 hours) in the thyroid bed was detected by diagnostic planar whole body scans in 93% and by posttherapy SPECT/CT imaging in 99% of subjects. Discrete RAI uptake foci were identified on the SPECT/CT imaging at Berry’s ligament (87%), at superior thyroid poles (79%), in paratracheal-lobar regions (67%), in isthmus-region (54%), and in pyramidal lobe (46%). Despite the residual foci, the nonstimulated thyroglobulin (Tg) prior to remnant ablation (with a median thyroid-stimulating hormone of 0.36 m IU/L) was <0.6 ng/mL in 53% and <1 ng/mL in 73% of cases. Conclusion After extracapsular total thyroidectomy, highly sensitive detection tools identify microscopic residual RAI avid foci in thyroid bed in the majority of patients. These foci can be classified as 1) neural-related and 2) capsule-related. These common residual foci have no relationship to postoperative Tg, suggesting that attempts at radical removal of thyroid tissue in these locations may not be warranted. PMID:25891354

  14. Global 3D Imaging of Yersinia ruckeri Bacterin Uptake in Rainbow Trout Fry

    PubMed Central

    Ohtani, Maki; Villumsen, Kasper Rømer; Koppang, Erling Olaf; Raida, Martin Kristian

    2015-01-01

    Yersinia ruckeri is the causative agent of enteric redmouth disease (ERM) in rainbow trout, and the first commercially available fish vaccine was an immersion vaccine against ERM consisting of Y. ruckeri bacterin. The ERM immersion vaccine has been successfully used in aquaculture farming of salmonids for more than 35 years. The gills and the gastrointestinal (GI) tract are believed to be the portals of antigen uptake during waterborne vaccination against ERM; however, the actual sites of bacterin uptake are only partly understood. In order to obtain insight into bacterin uptake during waterborne vaccination, optical projection tomography (OPT) together with immunohistochemistry (IHC) was applied to visualize bacterin uptake and processing in whole rainbow trout fry. Visualization by OPT revealed that the bacterin was initially taken up via gill lamellae from within 30 seconds post vaccination. Later, bacterin uptake was detected on other mucosal surfaces such as skin and olfactory bulb from 5 to 30 minutes post vaccination. The GI tract was found to be filled with a complex of bacterin and mucus at 3 hours post vaccination and the bacterin remained in the GI tract for at least 24 hours. Large amounts of bact