Caffeine robustly enhances transmitter release from the hippocampal mossy fiber terminals, although it remains uncertain whether calcium mobilization through presynaptic ryanodine receptors mediates this enhancement. In this study, we adopted a selective adenosine A1 blocker to assess relative contribution of A1 ...

Abstract. Two seemingly unrelated experimental treat-ments inhibit receptor mediated endocytosis: (a) deple-

Our previous studies showed that stimulation of adenosine A(1) receptors located in the nucleus of the solitary tract (NTS) exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and ?-adrenergic vasodilation vs. sympathetic and vasopressinergic vasoconstriction. Because NTS A(1) ...

Cellular/Molecular GABAA Receptor-Mediated Tonic Inhibition in Thalamic Neurons David W. Cope, United Kingdom TonicGABAA receptor-mediatedinhibitionistypicallygeneratedby subunit lateral geniculate nucleus (dLGN) and ventrobasal complex exhibit tonic inhibition. Focal application

Evidence for an Aryl Hydrocarbon Receptor-Mediated Cytochrome P450 Autoregulatory Pathway-1 cells through transient transfection with various cytochrome P450 isoforms. Expression of cytochromes P450 1A1, 1A2, or 1B1 reduced AhR-mediated luciferase reporter activity, whereas cytochrome P450 2

Previous studies of human and nonhuman primate lentiviral entry mechanisms indicate a predominant use of pH-independent pathways, although more recent studies of human immunodeficiency virus type 1 entry appear to reveal the use of a low-pH-dependent entry pathway in certain target cells. To expand the characterization of the specificity of lentiviral entry mechanisms, we have in the current study ...

The metabotropic GABA(B) and adenosine A(1) receptors mediate presynaptic inhibition through regulation of voltage-dependent Ca(2+) channels, whereas K(+) channel regulation is believed to have no role at the CA3-CA1 synapse. We show here that the inhibitory effect of baclofen (20 ?M) and ...

Sulindac, a widely used non-steroidal anti-inflammatory drug (NSAID), has been shown to inhibit chemically induced carcinogenesis in animal models. In the present study, we have investigated the molecular mechanism by which sulindac affects the activity and expression of the enzymes that mediate the initial detoxification steps of many environmental carcinogens, the ...

Angiogenesis, the process by which new blood vessels are formed from preexisting vasculature, is critical for vascular remodeling during development and contributes to the pathogenesis of diseases such as cancer. Prior studies from our laboratory demonstrate that the EphA2 receptor tyrosine kinase is a key regulator of angiogenesis in vivo. The EphA receptor-mediated ...

1. The adenosine A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA) induces hypotension in the anaesthetized rat. The present experiments were carried out to explore the role of mast cells in the response. 2. Intravenous injection of APNEA (1-30 micrograms kg-1 to rats in which the A3 receptor-mediated response had been isolated by pretreatment with ...

... brain, progesterone may mediate effects using the γ-aminobutyric acid (GABA) receptor [10]. Indeed, the existence of GABA ... and A. J. W. Hsueh. Identification of gamma-aminobutyric acid and its binding ...

Selective dopamine agonists acting at the D2 receptor (D2R) inhibit the toxicity caused by oxidative stress through a novel growth factor dependent and G protein independent signaling pathway. In response to oxidative stress, PC12 cells activate signaling...

In long-term space travel, the crew is exposed to microgravity and radiation that invoke potential hazards to the immune system. T cell activation is a critical step in the immune response. Receptor-mediated signaling is inhibited both in microgravity and...

The binding of antigen to the multicomponent T-cell receptor (TCR) activates several signal transduction pathways via coupling mechanisms that are poorly understood. One event that follows antigen receptor engagement is the activation of inositol phosphol...

Suppressor of cytokine signaling (SOCS) family proteins were initially identified as inhibiting cytokine signaling pathways through a negative feedback loop involving the inhibition of Janus kinase activity. More recent data suggest that SOCS proteins may also modulate signaling mediated through receptor tyrosine kinases. Krebs and Hilton discuss research ...

Adipocytes contain adenosine receptors, termed A1 receptors, which inhibit lipolysis by decreasing adenylate cyclase activity. The inhibition of lipolysis by adenosine agonists in vivo acutely suppresses the plasma concentrations of free fatty acids (FFA) and triglycerides. We have found that infusions of the ...

Although the neuromodulator adenosine plays an important role in many central nervous system physiological and pathological processes, the properties and mechanisms of extracellular adenosine production are still unclear. In previous work, we determined that two forms of adenosine release can be evoked in the molecular layer of the cerebellum: one independent of ionotropic glutamate receptor ...

GABA is the main inhibitory neurotransmitter in the adult forebrain, where it activates ionotropic type A and metabotropic type B receptors. Early studies have shown that GABA(A) receptor-mediated inhibition controls neuronal excitability and thus the occurrence of seizures. However, more complex, and at times unexpected, mechanisms of GABAergic signaling ...

GABA is the principal inhibitory neurotransmitter in the CNS, and acts via GABA_A and GABA_B receptors. Recently, a novel form of GABA_A receptor mediated inhibition, termed �tonic� inhibition, has been described. Whereas synaptic ...

Both GABA_B and muscarinic acetylcholine receptors (mAChRs) influence hippocampal-dependent mnemonic processing. Here the possibility of a direct interaction between GABA_B receptors and mAChR-mediated synaptic responses has been studied using intracellular recording in rat hippocampal slices.The GABA_B receptor agonist(?)-baclofen ...

Studies show that kidneys produce 2',3'-cAMP, 2',3'-cAMP is exported and metabolized to 2'-AMP and 3'-AMP, 2'-AMP and 3'-AMP are metabolized to adenosine, 2',3'-cAMP inhibits proliferation of preglomerular vascular smooth muscle cells (PGVSMCs) and glomerular mesangial cells (GMCs), and A(2B) (not A(1), A(2A), or A(3)) adenosine ...

The localization of cannabinoid (CB) receptors to GABAergic interneurons in the hippocampus indicates that CBs may modulate GABAergic function and thereby mediate some of the disruptive effects of marijuana on spatial memory and sensory processing. To investigate the possible mechanisms through which CB receptors may modulate GABAergic neurotransmission in the hippocampus, whole-cell voltage-clamp ...

were a competitive inhibitor of Pd phosphorylation, one would expect all of the inhibition curves of phosphorylation at maximal inhibition, PKA must be able to phosphorylate the Pd Gt complex. This noncompetitive . This binding sequesters G and inhibits both receptor-mediated activation of G and direct in- ...

The aryl hydrocarbon receptor (AhR) is expressed in estrogen receptor (ER)-positive ZR-75 breast cancer cells. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1A1 protein and mRNA levels and also activates inhibitory AhR-ER{alpha} crosstalk associated with hormone-induced reporter gene expression. In ZR-75 cells grown under hypoxia, ...

Bafilomycin A1 (baf), a specific inhibitor of vacuolar proton ATPases, is commonly employed to demonstrate the requirement of low endosomal pH for viral uncoating. However, in certain cell types baf also affects the transport of endocytosed material from early to late endocytic compartments. To characterize the endocytic route in HeLa cells that are ...

In freshly isolated spinal dorsal horn (DH) neurons (laminae I-IV) of the young rat, the effects of dynorphin A1-17, U-50,488H and U-69,593 on inward currents induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) were studied under whole-cell voltage-clamp conditions. When the cells were clamped to a holding potential ...

Amino acid- and inosine-induced germination of Bacillus cereus ATCC 14579 spores was reversibly inhibited in the presence of 3 mM undissociated sorbic acid. Exposure to high hydrostatic pressure, Ca-dipicolinic acid (DPA), and bryostatin, an activator of PrkC kinase, negated this inhibition, pointing to specific blockage of signal transduction in germinant ...

Amphetamine (AMPH) induces behavioral sensitization and neurotoxicity primarily by enhancing the dopamine-mediated neurotransmission. However, the involvement of the N-methyl-D-aspartate (NMDA) receptor in AMPH-induced neuropathology is also known. Recent investigation has found that high concentration of dopamine could inhibit NMDA receptor-mediated ...

Botulinum neurotoxin (BoNT) heavy chain (Hc) facilitates receptor-mediated endocytosis into neuronal cells and transport of the light chain (Lc) protease to the cytosol where neurotransmission is inhibited as a result of SNARE protein cleavage. Here we show that the role of BoNT Hc in cell intoxication can be replaced by commercial lipid-based and ...

Recently, this laboratory identified a proton-coupled folate transporter (PCFT), with optimal activity at low pH. PCFT is critical to intestinal folate absorption and transport into the central nervous system because there are loss-of-function mutations in this gene in the autosomal recessive disorder, hereditary folate malabsorption. The current study addresses the role PCFT might play in ...

Gamma-aminobutyric acid (GABA)-ergic inhibition is important in the function of the visual cortex. In a previous study, we reported a developmental increase in GABA(A) receptor-mediated inhibition in the rat visual cortex from 3 to 5 weeks of age. Because this developmental increase is crucial to the regulation of the induction of ...

Gamma-aminobutyric acid (GABA)-ergic inhibition is important in the function of the visual cortex. In a previous study, we reported a developmental increase in GABA_A receptor-mediated inhibition in the rat visual cortex from 3 to 5 weeks of age. Because this developmental increase is crucial to the regulation of ...

The densities of total and M1 muscarinic receptors were measured using the muscarinic receptor antagonists {sup 3}H-quinuclidinyl benzilate and {sup 3}H-pirenzepine, respectively. Thus, the difference between the density of {sup 3}H-quinuclidinyl benzilate and {sup 3}H-pirenzepine binding sites represents the density of M2 sites. In addition, there is no observable change in either ...

Cortisol was reported to downregulate body-fluid Ca²⁺ levels in mammals but was proposed to show hypercalcemic effects in teleostean fish. Fish, unlike terrestrial vertebrates, obtain Ca²⁺ from the environment mainly via the gills and skin rather than by dietary means, and have to regulate the Ca²⁺ uptake functions to cope with ...

Adenosine serves as a homeostatic factor, regulating hippocampal activity through A(1) receptor-mediated inhibition. Gamma frequency oscillations, associated with cognitive functions, emerge from increased network activity. Here we test the hypothesis that hippocampal gamma oscillations are modulated by ambient ...

All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be expressed in cardiomyocytes. There is also increasing evidence that optimal adenosine cardioprotection requires activation of more than one receptor subtype. The purpose of this study was to determine whether adenosine A(2A) and/or A(2B) receptors modulate ...

Aberrant ?-aminobutyric acid type A (GABA(A)) receptor-mediated inhibition in cortico-thalamic networks remains an attractive mechanism for typical absence seizure genesis. Using the whole-cell patch clamp technique we examined 'phasic' and 'tonic' GABA(A) inhibition in thalamocortical neurons of somatosensory (ventrobasal, VB) ...

Histamine regulates functions via four receptors (HRH1, HRH2, HRH3, and HRH4). The d-myo-inositol 1,4,5-trisphosphate (IP₃)/Ca²⁺/protein kinase C (PKC)/mitogen-activated protein kinase pathway regulates cholangiocarcinoma growth. We evaluated the role of HRH3 in the regulation of cholangiocarcinoma growth. Expression of HRH3 in intrahepatic and ...

Botulinum neurotoxin (BoNT) potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated ...

Botulinum neurotoxin (BoNT) potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of ...

Conventional peritoneal dialysis solutions (PDS) are vasoactive. This study was conducted to identify vasoactive components of PDS and to describe quantitatively such vasoactivity. Anesthetized nonheparinized rats were monitored continuously for hemodynamics while the microvasculature of the jejunum was studied with in vivo intravital microscopy. In separate experiments, vascular reactivity of rat ...

Human CYP2B6 has been thought to account for a minor portion (< 1%) of total hepatic cytochrome P450 (CYP) content and to have a minor function in human drug metabolism. Recent studies, however, indicate that the average relative contribution of CYP2B6 to total hepatic CYP content ranges from 2% to 10%. An increased interest in CYP2B6 research has been stimulated by the identification of an ...

Dopamine D1-like receptors, composed of D1 and D5 receptors, have been documented to modulate glutamate-mediated fast excitatory synaptic neurotransmission. Here, we report that dopamine D1 receptors modulate NMDA glutamate receptor-mediated functions through direct protein-protein interactions. Two regions in the D1 receptor carboxyl tail can directly and selectively couple ...

Emerging evidence reveals that pattern-recognition receptors (PRRs), Toll-like receptors (TLRs) and Nucleotide-binding oligomerization domain proteins (NODs) mediate both infection-induced and sterile inflammation by recognizing pathogen-associated molecular patterns (PAMPs) and endogenous molecules...

-mediated tonic conductance that contributes 80% of the total GABAA receptor-mediated transmission. Consequently, although etomidate enhances inhibition in both neuronal types, the effect of this anesthetic on the tonic, clinically relevant concentrations (30 nM to 3 M) increases the tonic conductance of VB neurons

Atherosclerosis is an inflammatory process that leads to the onset of cardiovascular disease. The scavenger receptor-mediated uptake of oxLDL by macrophages leads to foam cell formation, which is an initial event in the formation of atherosclerotic fatty streak lesions. In this report, the mechanism...

Toluene, an industrial organic solvent, is voluntarily inhaled as drug of abuse. Because inhibition of N-methyl-d-aspartate (NMDA) receptors is one of the possible mechanisms underlying developmental neurotoxicity of toluene, the purpose of the present study was to examine the effects of toluene exposure during two major neurodevelopmental stages, brain growth spurt and ...

Prolactin-releasing peptide (PrRP) is an RF-amide peptide that is believed to be the physiological ligand for the G-protein coupled receptor GPR10. This receptor is highly expressed in the GABAergic principal neurons of the reticular thalamic nucleus (RTN), but the cellular and physiological effects of receptor activation on thalamic function are not yet clear. The present study examined the ...

... Accession Number : ADA071620. Title : Receptor-mediated Internalization and Degradation of Diphtheria Toxin by Monkey Kidney Cells. ...

ABSTRACT: BACKGROUND: It is known that retinoid receptor function is attenuated during T cell activation, a phenomenon that involves actin remodeling, suggesting that actin modification may play a role in such inhibition. Here we have investigated the role of actin dynamics and the effect of actin cytoskeleton modifying agents on retinoid receptor-mediated ...

The entorhinal cortex (EC) is regarded as the gateway to the hippocampus and thus is essential for learning and memory. Whereas the EC expresses a high density of GABA(B) receptors, the functions of these receptors in this region remain unexplored. Here, we examined the effects of GABA(B) receptor activation on neuronal excitability in the EC and spatial learning. Application of baclofen, a ...

One week oral flurazepam (FZP) administration in rats results in reduced GABA_A receptor-mediated synaptic transmission in CA1 pyramidal neurons associated with benzodiazepine tolerance in vivo and in vitro. Since voltage-gated calcium channel (VGCC) current density is enhanced 2-fold during chronic FZP treatment, the role of L-type VGCCs in regulating ...

Prednisolone, at concentrations between 2�78 � 10^?6 M (1 ?g/ml) and 1�39 � 10^?8 M (5 � 10^?3 ?g/ml) exerts an inhibitory effect on the phagocytosis of latex particles by normal human polymorphonuclear leucocytes in vitro as assessed by electron microscopical analysis. This inhibition appears to be ...

Experimental evidence in animal models suggests that adenosine is involved in the regulation of digestive functions. This study examines the influence of adenosine on the contractile activity of human colon. Reverse transcription-polymerase chain reaction revealed A(1) and A(2a) receptor expression in colonic neuromuscular layers. Circular muscle ...

Isorhynchophylline is a major oxindole alkaloid found in Uncaria species which have long been used in traditional Chinese medicine. Here, we investigated the effects of isorhynchophylline and isorhynchophylline-related alkaloids on 5-hydroxytryptamine (5-HT) receptor-mediated behavioural responses in mice and 5-HT-evoked current responses in Xenopus oocytes expressing 5-HT2A ...

Striatal GABAergic microcircuits are critical for motor function, yet their properties remain enigmatic due to difficulties in targeting striatal interneurons for electrophysiological analysis. Here, we use Lhx6-GFP transgenic mice to identify GABAergic interneurons and investigate their regulation of striatal direct- and indirect-pathway medium spiny neurons (MSNs). We find that the two major ...

Striatal GABAergic microcircuits are critical for motor function, yet their properties remain enigmatic due to difficulties in targeting striatal interneurons for electrophysiological analysis. Here, we utilize Lhx6-GFP transgenic mice to identify GABAergic interneurons and investigate their regulation of striatal direct- and indirect-pathway medium spiny neurons (MSNs). We find that the two major ...

Heat shock proteins (HSPs) like glycoprotein (gp)96 (glucose-regulated protein 94 [grp94]) are able to induce specific cytotoxic T lymphocyte (CTL) responses against cells from which they originate. Here, we demonstrate that for CTL activation by gp96-chaperoned peptides, specific receptor-mediated uptake of gp96 by antigen-presenting cells (APCs) is required. Moreover, we ...

Traumatic brain injury (TBI) is a risk factor for the development of epilepsy, which can occur months to years after the insult. The hippocampus is particularly vulnerable to the pathophysiological effects of TBI. Here, we determined whether there are long-term changes in inhibition in the dentate gyrus that could contribute to the progressive susceptibility to seizures after ...

The present invention relates to compositions and methods for cancer therapeutics. In particular, the present invention provides compositions and methods for inhibiting cancer metastasis by inhibiting cyclin A1.

BackgroundRasagiline, a new drug developed to treat Parkinson's disease, is known to inhibit monoamine oxidase B. However, its metabolite R-(-)-aminoindan does not show this kind of activity. The present series of in vitro experiments using the rat hippocampal slice preparation deals with effects of both compounds on the pyramidal cell response after electric stimulation of ...

In vitro experiments were performed to examine the effect of cadmium on adherent phagocytic cell populations. The authors were able to demonstrate, in vitro, a phagocytic defect that was originally observed in an in vivo system. Using in vitro methodologies, cadmium was found to inhibit opsonin-dependent but not opsonin-independent phagocytosis in two different populations of ...

Previously, we reported that prostanoid TP receptor mediates the inhibition of electrically evoked noradrenaline release from gastric sympathetic nerves in rats. Prostanoid TP receptor has been shown to activate phospholipase C (PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-triphosphate ...

Receptor-mediated agonists, such as FMLP, induce an early, phospholipase D (PLD)-mediated accumulation of phosphatidic acid (PA) which may play a role in the activation of NADPH oxidase in human PMN. We have determined the effect of changes in PA production on O2 consumption in intact PMN and the level of NADPH oxidase activity measured in a cell-free assay. Pretreatment of ...

Adenosine A(2) receptors have been suggested to modulate tubuloglomerular feedback (TGF) responses by counteracting adenosine A(1) receptor-mediated vasoconstriction, but the mechanisms are unclear. We tested the hypothesis that A(2A) receptor activation blunts TGF by release of nitric oxide in the juxtaglomerular apparatus (JGA). ...

Lithium ion, which inhibits hydrolytic degradation of inositol monophosphates, is the most common therapeutic agent used in the control of bipolar disorder. There exists evidence that elevated elemental vanadium levels may play an etiological role in at least some forms of manic-depression. Here we demonstrate that vanadate treatment of intact cells from several different ...

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of the central nervous system. Symptomatic and presymptomatic ALS patients demonstrate cortical hyperexcitability, which raises the possibility that alterations in inhibitory gamma-aminobutyric acid (GABA)ergic system could underlie this dysfunction. Here, we studied the GABAergic system in cortex using patch-clamp ...

1. The potency, relative efficacy and selectivity of a series of kappa-opioid receptor agonists at the mu-, delta- and kappa-opioid receptors mediating inhibition of electrically-induced (radiolabelled) neurotransmitter release from superfused rat brain slices was determined. 2. With regard to their potencies at ...

KCNQ1 is co-assembled with KCNE1 subunits in the heart to form the cardiac delayed rectifier K⁺ current (IKs), which is one of the main currents responsible for myocyte repolarization. The most commonly inherited form of cardiac arrhythmias, long-QT syndrome type 1 (LQT1), is due to mutations on KCNQ1. Gq-coupled receptors (GqPCRs) are known to mediate positive inotropism in ...

Page 1. Extraction and Inhibition of Enzymatic Activity of Botulinum Neurotoxins/A1, /A2, and /A3 by a Panel of Monoclonal Anti-BoNT/A Antibodies ...

The modulatory effect of Total Flavone of Abelmoschus manihot L. Medic (TFA) on NMDA-activated current (I(NMDA)) was investigated in cultured rat hippocampal neurons using the whole-cell patch-clamp technique. TFA rapidly and reversibly inhibited the I(NMDA) in a concentration-dependent manner. Furthermore, TFA non-competitively inhibited the I(NMDA) by ...

Estrogen deficiency causes bone loss, which can be prevented by estrogen replacement therapy. Using a recently developed technique for isolation of highly purified mammalian osteoclasts, we showed that 17 beta-estradiol (E2) was able to directly inhibit osteoclastic bone resorption. At concentrations effective for inhibiting bone resorption, E2 also ...

Topiramate [2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] is a structurally novel antiepileptic drug that has broad efficacy in epilepsy, but the mechanisms underlying its therapeutic activity are not fully understood. We have found that topiramate selectively inhibits GluK1 (GluR5) kainate receptor-mediated excitatory postsynaptic ...

Aberrant ?-aminobutyric acid type A (GABA_A) receptor-mediated inhibition in cortico-thalamic networks remains an attractive mechanism for typical absence seizure genesis. Using the whole-cell patch clamp technique we examined �phasic� and �tonic� GABA_A inhibition in thalamocortical ...

Action mechanism of lipopolysaccharide (LPS), interleukin-1? (IL-1?), and lysophosphatidic acid (LPA) to regulate motility, an important process of astrogliosis, was investigated in rat astrocytes. While LPA exerted no significant effect on the cell migration, the prior treatment of the cells with LPS or IL-1? resulted in the appearance of migration activity in response to LPA. The LPS induction ...

Human peripheral blood granulocytes previously were found to contain opioid delta 2-receptors mediating stimulation by opioid peptides of chemotaxis. Studies presented in this work indicate that granulocytes also contain opiate alkaloid-selective, opioid peptide-insensitive receptors mediating ...

Rod bipolar cells relay visual signals evoked by dim illumination from the outer to the inner retina. GABAergic and glycinergic amacrine cells contact rod bipolar cell terminals, where they modulate transmitter release and contribute to the receptive field properties of third order neurones. However, it is not known how these distinct inhibitory inputs affect rod bipolar cell output and subsequent ...

Chronic activation or inhibition of cannabinoid receptors (CB1) leads to continuous suppression of neuronal plasticity in hippocampus and other brain regions, suggesting that endocannabinoids may have a functional role in synaptic processes that produce state-dependent transient modulation of hippocampal cell activity. In support of this, it has previously been shown in vitro ...

1 Administration of the 5-HT1B receptor agonist m-chlorophenylpiperazine (m-CPP) to rats produces dose-dependent decreases in locomotor activity and food intake. 2 The locomotor suppressant effect of m-CPP was inhibited by the 5-hydroxytryptaminergic antagonist, metergoline, but not by phentolamine, propranolol, clonidine, or haloperidol. 3 The locomotor suppressant effects of ...

The stable transcription factor ?FosB is induced in the nucleus accumbens (NAc) by chronic exposure to several drugs of abuse, and transgenic expression of ?FosB in the striatum enhances the rewarding properties of morphine and cocaine. However, the mechanistic basis for these observations is incompletely understood. We used a bitransgenic mouse model with inducible expression of ?FosB in dopamine ...

Background and Purpose:Cannabinoids are associated with analgesia in acute and chronic pain states. A spectrum of central cannabinoid (CB₁) receptor-mediated motor and psychotropic side effects limit their therapeutic potential. Here, we investigate the analgesic effect of the palmitoylethanolamide (PEA) analogue, palmitoylallylamide (L-29), which via ...

The authors previously reported that adenosine (A) stimulates secretion of phosphatidylcholine (PC), the major component of surfactant, in type II pneumocytes. To determine how this effect is mediated we examined the effect of P{sub 1} purinoceptor agonists -N{sup 6}-phenylisoprpyl-A (PIA), 5{prime}-N-ethylcarboxyamido-A (NECA), 2-chloro-A (CA) - and antagonists - theophylline (T) and ...

Prostaglandins are lipid signaling intermediates released by keratinocytes in response to ultraviolet irradiation (UVR) in the skin. The main prostaglandin released following UVR is PGE{sub 2}, a ligand for 4 related G-protein-coupled receptors (EP{sub 1}, EP{sub 2}, EP{sub 3} and EP{sub 4}). Our previous work established that PGE{sub 2} stimulates melanocyte dendrite formation through activation ...

BackgroundCadmium (Cd) is a potent nephrotoxicant that impairs the reabsorptive and secretory functions of the renal proximal tubule, leading to albuminuria.ObjectivesTo gain insights into the mechanisms of Cd-induced albuminuria, we investigated effects of Cd on the expression of megalin and chloride channel 5 (ClC5), two key players in albumin- receptor�mediated ...

(1) Vasopressin (VP), or antidiuretic hormone, is secreted in response to either increases in plasma osmolality (very sensitive stimulus) or to decreases in plasma volume (less sensitive stimulus). Its normal plasma level is very low (about 1 pg/ml, i.e. 10(-12) M), close to the detection limit of present immunoassays, and distinct antidiuretic effects are observed after infusion of small ...

Muscarinic stimulation of mucus secretion, as measured by the release of ({sup 3}H)glycoprotein, was studied in explants from the tracheal epithelium of weanling swine. The mucus glycoprotein secretion was transient, ceasing within the first 10 min of a continuous exposure to 100 {mu}M ACh. Increasing the solutions' osmotic pressure did not alter basal mucus glycoprotein secretion. Mucus ...

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited arrhythmia syndrome in which drug therapy is often ineffective. We discovered that flecainide prevents arrhythmias in a mouse model of CPVT by inhibiting cardiac ryanodine receptor-mediated Ca(2+) release and thereby directly targeting the underlying molecular ...

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited arrhythmia syndrome in which drug therapy is often ineffective. We discovered that flecainide prevents arrhythmias in a mouse model of CPVT by inhibiting cardiac ryanodine receptor�mediated Ca²⁺ release and thereby directly targeting the ...

1. Stimulation of the surviving afferents in the stratum radiatum of the CA1 area in kainic acid-lesioned hippocampal slices produced graded epileptiform activity, part of which (> 20%) involved the activation of N-methyl-D-aspartate (NMDA) receptors. There was also a failure of synaptic inhibition in this region. In this preparation, we have tested the effects of ...

Targeting death receptor-mediated apoptosis has emerged as an effective strategy for cancer therapy. However, certain types of cancer cells are intrinsically resistant to death receptor-mediated apoptosis. In an effort to identify agents that can sensitize cancer cells to death receptor-induced apoptosis, we have identified Honokiol, a natural product with ...

The glucocorticoids are the most potent anti-inflammatory drugs that we possess and are effective in a wide variety of diseases. Although their action is known to involve receptor mediated changes in gene transcription, the exact mechanisms whereby these bring about their pleiotropic action in inflammation are yet to be totally understood. Whilst many ...

Abstract 3,3',4,4'-Tetrachlorobiphenyl (TCB) can induce and inhibit cytochrome P450 1A1 (CYP1A1) in vertebrates. TCB may also suppress CYP1A1 protein levels, but the mechanism is unknown. This study examined transcriptional and translational aspects of ...

Two-pore-domain K⁺ channels provide neuronal background currents that establish resting membrane potential and input resistance; their modulation provides a prevalent mechanism for regulating cellular excitability. The so-called TASK channel subunits (TASK-1 and TASK-3) are widely expressed, and they are robustly inhibited by receptors that signal ...

FcR-like (FCRL) 2 is a transmembrane protein with immunomodulatory potential that is preferentially expressed by memory B cells in humans. It has two consensus ITIMs in addition to a putative ITAM sequence in its cytoplasmic domain. We have confirmed the cellular distribution of FCRL2 and analyzed its functional potential to show that coligation with the BCR leads to tyrosine phosphorylation of ...

PL017 and dynorphin A1-17 were shown previously to cause a marked increase and a profound decrease in body temperature (Tb), respectively. In this study, we examined whether an antisense (AS) oligodeoxynucleotide (oligo) against cloned mu or kappa opioid receptors could block PL017- or dynorphin A-induced body temperature changes. Treatment with an AS ...

... Title : Estrogen Receptor-Mediated Transcription in Vitro. ... Abstract : Estrogen receptor (ER) is a ligand-activated transcription activator. ...

... Title : Estrogen Receptor-Mediated Transcription In Vitro. ... Abstract : Estrogen receptor (ER) is a ligand-activated transcription activator. ...

... Title : Estrogen Receptor-Mediated Transcription In Vitro. ... Abstract : Estrogen receptor (ER) is a ligand activated transcription activator. ...

... Award Number: W81XWH-04-1-0823 TITLE: Androgen Receptor-Mediated Escape Mechanisms from Androgen Ablation Therapy ...

... Title : Androgen Receptor-Mediated Escape Mechanism from Androgen Ablation ... is the key master regulator (transcription factor) that determines ...

1. The 5-hydroxytryptamine (5-HT) receptors mediating vasoconstriction in isolated human small muscular pulmonary arteries (SMPAs) were determined using techniques of wire myography and reverse transcription-polymerase chain reaction (RT - PCR). 2. The agonists 5-HT, 5-carboxamidotryptamine (5-CT, unselective for 5-HT1 receptors) and sumatriptan (selective ...

The hippocampus is essential for the formation of certain types of memory, and synaptic plasticity such as long-term potentiation (LTP) is widely accepted as a cellular basis of hippocampus-dependent memory. Although LTP in both perforant path-dentate gyrus (DG) granule cell and CA3-CA1 pyramidal cell synapses is similarly dependent on activation of postsynaptic N-methyl-D-aspartate receptors, ...

The authors have characterized the actions of taxol, a novel drug promoting microtubule formation, on /sup 45/Ca++ uptake and catecholamine release by isolated and cultured bovine adrenal chromaffin cells. The effects of taxol are compared with corresponding actions of vinblastine. Measurements have also been made of the effects of microtubule-active drugs on the dynamic pattern of release by ...

BackgroundRegular aerobic exercise improves large artery compliance in middle-aged and older humans. However, the underlying mechanisms are unknown. We tested the hypothesis that the improved central arterial compliance with endurance training is mediated by decreased ?-adrenergic tone and/or increased endothelial function.MethodsSeven sedentary healthy adults (60�3 yr) underwent systemic ...

Serum amyloid A (SAA) is a major acute phase protein involved in multiple physiological and pathological processes. This study provides experimental evidence that CD36, a phagocyte class B scavenger receptor, functions as a novel SAA receptor mediating SAA proinflammatory activity. The uptake of Alexa Fluor� 488 SAA as well as of other well established ...

SummaryNeurons use neurotransmitters to communicate across synapses, constructing neural circuits in the brain. AMPA-type glutamate receptors are the predominant excitatory neurotransmitter receptors mediating fast synaptic transmission. AMPA receptors localize at synapses by forming protein complexes with transmembrane AMPA receptor regulatory proteins ...

Mammalian cells have been shown to internalize oligonucleotide-functionalized gold nanoparticles (DNA-Au NPs or siRNA-Au NPs) without the aid of auxiliary transfection agents and use them to initiate an antisense or RNAi response. Previous studies have shown that the dense monolayer of oligonucleotides on the nanoparticle leads to the adsorption of serum proteins and facilitates cellular uptake. ...

We have found that galantamine, but not donepezil, reversed isolation rearing-induced deficits of prepulse inhibition (PPI) via an activation of muscarinic M(1) receptors. To explain this difference, the present study examined the effects of these acetylcholinesterase inhibitors on muscarinic receptor-mediated responses in in vitro and in vivo systems. ...

Apical membrane Cl^- channels control the rate of transepithelial Cl^- secretion in airway epithelia. cAMP-dependent protein kinase and protein kinase C regulate Cl^- channels by phosphorylation; in cystic fibrosis cells, phosphorylation-dependent activation of Cl^- channels is defective. Another important signaling system involves arachidonic acid, which is released from cell membranes during ...

Gamma-frequency oscillations depend on phasic synaptic GABA_A receptor-mediated inhibition to synchronize spike timing. The spillover of synaptically-released GABA can also activate extrasynaptic GABA_A receptors, and such tonic inhibition may also contribute to modulating network dynamics. ...

The Nogo receptor and paired immunoglobulin-like receptor B (PIR-B) are receptors for three myelin-derived axon-growth inhibitors, including myelin-associated glycoprotein (MAG). In this study, we report that the p75 receptor is required for the signal transduction of PIR-B, which interacted with p75 upon ligand binding. In addition, p75 was required for activation of Src homology 2-containing ...

Hormones such as insulin are transported from the interior to the exterior of blood vessels. Whether endothelial cells, which line the inner walls of blood vessels have a role in this transport of hormones is not clear, but it is known that endothelial cells can internalize and release insulin rapidly with little degradation. The transport of iodine-125-labeled insulin was measured directly ...

We describe a transcriptional mechanism regulating the expression of Dnmt1 by nuclear receptors. We show that ERR? functions as a transcriptional activator of mouse and human Dnmt1 expression by direct binding to its response elements (ERE1/ERE2) in the dnmt1/DNMT1 promoters. The induction of Dnmt1 by ERR? is repressed by SHP through SHP inhibition of ERR? transactivity, ...

The effects of docosahexaenoic acid (DHA) and other fatty acids on P2X-receptor-mediated inward currents in rat nodose ganglion neurons were studied using the nystatin perforated patch-clamp technique. DHA accelerated the desensitization rate of the ATP-induced current. DHA showed use-dependent inhibition of the peak ATP-induced current. Other polyunsaturated fatty acids, such ...

A yeast two-hybrid assay has identified an androgen-dependent interaction of androgen receptor (AR) with amino-terminal enhancer of split (AES), a member of the highly conserved Groucho/TLE family of corepressors. Full-length AR, as well as the N-terminal fragment of AR, showed direct interactions with AES in in vitro protein-protein interaction assays. AES specifically ...

?-Aminobutyric acid type A (GABA_A) receptors mediate the majority of fast synaptic inhibition in the mammalian brain, controlling activity both at the network and cellular level. The diverse functions of GABA in the central nervous system are matched not just by the heterogeneity of GABA_A ...

The addition of monoclonal antibodies to the antigen receptor complex on the malignant human T-cell line Jurkat generates increases in inositol trisphosphate and in the concentration of cytoplasmic free calcium. Exposure of Jurkat cells to cholera toxin for 3 hr inhibited these receptor-mediated events and led to a selective, partial loss of the antigen receptor complex from ...

mAb were selected that inhibited IgE-mediated histamine release from human basophils. The two mAb, HB 9AB6 and HB 10AB2, are of the IgG1 subclass and have a 50% inhibitory concentration of 0.16 to 1.1 micrograms/ml. The mAb required several hours of incubation with the basophils at 37 degrees C to induce maximum inhibition. Neither mAb directly released ...

The immunomodulatory role of endogenous opioid peptides released during stress has been extensively studied in mammals, but least explored in lower vertebrates. The present in vitro study for the first time reports the specific opioid receptor-mediated immunomodulatory role of dynorphin-A((1-17)) in ectotherms. Dynorphin-A((1-17)) had ...