Low Ethanol Sensitivity and Increased Ethanol Consumption in Mice Lacking Adenosine A2A Receptors2AR / ) mice. In the present report, we further characterize the role of adenosine A2A receptors be- tween the two genotypes. The ...

The ubiquitous adenosine A2-like binding protein obscures the binding properties of adenosine receptors assayed with 5'-N-({sup 3}H)ethylcarboxamidoadenosine (({sup 3}H)NECA). To solve this problem, we developed a rapid and simple method to separate adenosine ...

The influence of brain inflammation upon neuronal adenosine A2B receptors Susanna Rosi, Kristin Mc results suggest that anti-inflammatory therapies can slow the onset of AD. Adenosine, acting at type-2 for adenosine A2B ...

... PARKINSONS DISEASE, SYMPOSIA, ADENOSINE, STROKES(CEREBRAL), CLINICAL TRIALS, ALZHEIMER DISEASE, MENTAL DISORDERS ...

In pursuit of an improved understanding and treatment of Parkinson's disease (PD) and related neuropsychiatric disease we have held a translational research conference entitled, 'Targeting Adenosine A2A Receptors in Parkinson's Disease and other CNS Disor...

Adenosine is an important regulatory metabolite and an inhibitor of platelet activation. Adenosine released from different cells or generated through the activity of cell-surface ectoenzymes exerts its effects through the binding of four different G-protein-coupled adenosine receptors. In platelets, binding of A(2) ...

molecule adenosine. In mammals, adenosine assumes an essential role in regulating innate and acquired, but only adenosine is able to completely suppress immune responses (N�meth et al., 2006). The immunoregulatory attributes of adenosine are mediated via four transmembrane adenosine ...

Recent advances in the pharmacology, neurotoxicology and epidemiology of the adenosine A2A receptor have provided evidence that A2A receptor antagonists (including caffeine) may offer therapeutic benefits in Parkinson's disease (PD) at multiple levels. No...

The �omnipresence� of adenosine in all nervous system cells (neurons and glia) together with the intensive release of adenosine following insults, makes adenosine as a sort of �maestro� of synapses leading to the homeostatic coordination of brain function. Besides direct actions of adenosine on the ...

Because A2 adenosine receptor activation stimulates adenylate cyclase and cyclic AMP induces 5'-nucleotidase expression in rat mesangial cells, we examined the effect of adenosine and its analogs on 5'-nucleotidase activity in these cells. A2 ...

Importance of making available selective adenosine receptor antagonists is boosted by recent findings of adenosine involvement in many CNS dysfunctions. In the present work a series of 8-bromo-9-alkyl adenines are prepared and fully characterized in radioligand binding assays or functional cyclase experiments in respect to their ...

The important role that extracellular adenosine plays in many physiological processes is mediated by the adenosine class of G protein-coupled receptors, a class of receptors that also responds to the antagonist caffeine, the most widely used pharmacological agent in the world. The crystallographic model of the ...

... modify the affinity for the hormone or ligand ... intake, suggesting that female hormones may prevent the ... that treatment with A2A antagonists may be a ...

organization of the adenosine A2A receptor gene by molecular and bioinformatics analyses. Brain Res. 2004 Mar, Peterfreund RA, Fuxe K, Vincent JD, Lledo PM. Activation of adenosine A1 and A2A receptors modulates dopamine, Gies EK, Gelb CR, Peterfreund RA. Agonist-induced ...

Adenosine A(2A) receptors seem to exist in typical (more in striatum) and atypical (more in hippocampus and cortex) subtypes. In the present study, we investigated the affinity of two adenosine A(2A) receptor antagonists, ST1535 [2 ...

Space flight and gravitational stress can alter innate immune function. Parabolic flights (PFs) as a model for short-term gravitational changes prime the cytotoxic capability of polymorphonuclear leukocytes (PMNs). In view of the emerging role of adenosine in the regulation of innate immune responses, we examined the potency of adenosine to control the ...

The excitatory action of brain-derived neurotrophic factor (BDNF) on synaptic transmission is triggered by adenosine A2A receptor activation. Since high-frequency neuronal firing, such as that inducing long-term potentiation (LTP), favours both A2A ...

In this paper we review some novel aspects related to the way adenosine A(2A) receptors (A(2A)R) modulate the action of BDNF or its high-affinity receptors, the TrkB receptors, on synaptic transmission and plasticity, as well as ...

A(2A) adenosine receptors are considered an excellent target for drug development in several neurological and psychiatric disorders. It is noteworthy that the responses evoked by A(2A) adenosine receptors are regulated by D(2) dopamine receptor ligands. ...

Figure 4: Extracellular adenosine signaling during acute lung injury. Legend: Adenosine (A) signaling during acute lung injury can involve any of four adenosine receptors: the A1, A2A, A2B, and A3 receptors. ...

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 ...

Cellular/Molecular Presynaptic Control of Striatal Glutamatergic Neurotransmission by Adenosine A1 of debate. In the present study, we demonstrate that heteromerization of adenosine A1 receptors (A1Rs) and A2A receptors (A2ARs) allows adenosine to exert ...

Few signaling molecules have the potential to influence the developing mammal as the nucleoside adenosine. Adenosine levels increase rapidly with tissue hypoxia and inflammation. Adenosine antagonists include the methylxanthines caffeine and theophylline. The receptors that transduce adenosine ...

Background and purpose. This study was undertaken to investigate the role of adenosine in the modulation of the contractility in mouse duodenum and to characterize the adenosine receptor subtypes involved. Experimental approach. RT-PCR was used to investigate the expression of mRNA encoding for A(1) , ...

It has been hypothesized that an interaction among adenosine A(1) receptors, protein kinase C (PKC) activation, and ATP-sensitive potassium channels (K(ATP)) mediates ischemic preconditioning in experiments on different animal species. The purpose of this study was to determine if activation of K(ATP) is functionally coupled to A(1) ...

In the kidney, defects in the regulation of urine salt excretion can result in extracellular fluid volume expansion, leading to salt-sensitive hypertension. Previous studies have demonstrated that when rats are maintained on a high sodium chloride (NaCl) diet, adenosine production increases in the renal medulla with parallel changes in adenosine ...

Adenosine is an important paracrine agent regulating renal vascular tone via adenosine A(1) and A(2) receptors. While A(2B) receptor message and protein have been localized to preglomerular vessels, functional evidence on the role of A(2B) receptors in ...

This review focuses on the potential role of site- and event-selective adenosinergic drugs in the treatment of cardiovascular diseases. Adenosine is released from the myocardium and vessels in response to various forms of stress and acts on four receptor subtypes (A1, A2A, ...

It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxy-phenylisopropyladenosine ((R)-AHPIA) into the A1 adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of cellular cAMP levels. In ...

In the past decades, increased concentrations of the signaling molecule adenosine have been shown to play an important role in the prevention of tissue damage evoked by several stressful circumstances. During systemic inflammation, the circulating adenosine concentration increases rapidly, even up to 10-fold in septic shock patients. By binding to specific ...

Three new X-ray structures of a thermostabilized A(2A) adenosine receptor in complex with different antagonists reported by Dor� et�al. in this issue have advanced the understanding of molecular recognition for this receptor. PMID:21893281

Adenosine is an important cerebral vasodilator, but mediating mechanisms are not understood. We investigated the expression of adenosine receptor subtypes in isolated cerebral arterial muscle cells (CAMCs), and their role in adenosine-induced superoxide (O(2)(-)) generation and reduction in cerebral arterial tone. ...

1. A degree of ambiguity and uncertainty exists concerning the distribution of mRNAs encoding the four cloned adenosine receptors. In order to consolidate and extent current understanding in this area, the expression of the adenosine receptors has been examined in the rat by use of in situ hybridisation and the ...

We wished to determine whether adenosine, a purine nucleotide, modulates activity of respiratory cilia and, to this end, we studied cultured rabbit tracheal epithelium in response to adenosine and related substances in vitro. Ciliary beat frequency (CBF) as determined by a photoelectric method was depressed by adenosine (10(-3) M), the ...

Mucociliary clearance, vital to lung clearance, is dependent on cilia beat frequency (CBF), coordination of cilia, and the maintenance of periciliary fluid. Adenosine, the metabolic breakdown product of ATP, is an important modulator of ciliary motility. However, the contributions of specific adenosine receptors to key airway ciliary ...

The (-)-(11R,2'S)-enantiomer of the antimalarial drug mefloquine has been found to be a reasonably potent and moderately selective adenosine A(2A) receptor antagonist. Further investigation of this compound has led to the discovery of a series of keto-aryl thieno[3,2-d]pyrimidine derivatives, which are potent and ...

Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate ...

Adenosine is a signalling molecule that modulates cellular activity in the central nervous system and peripheral organs via four G protein-coupled receptors designated A(1), A(2A), A(2B), and A(3). This review surveys the literature on the role of ...

Few studies to date have looked at the effects of caffeine on synaptic plasticity, and those that did used very high concentrations of caffeine, whereas the brain concentrations attained by regular coffee consumption in humans should be in the low micromolar range, where caffeine exerts pharmacological actions mainly by antagonizing adenosine receptors. ...

Purines are important modulators of bone cell biology. ATP is metabolized into adenosine by human primary osteoblast cells (HPOC); due to very low activity of adenosine deaminase, the nucleoside is the end product of the ecto-nucleotidase cascade. We, therefore, investigated the expression and function of adenosine ...

In patients with paroxysmal non-kinesigenic dyskinesias, episodes of dystonia can be provoked by stress and also by methylxanthines (e.g. caffeine), which inhibit adenosine A(1)/A(2A) receptors. In the dt(sz) mutant hamster, a model of this movement disorder, adenosine A(1) ...

Adenosine is released during tissue injury, ischemia and tumor growth, and promotes angiogenesis. Because mast cells accumulate in the proximity of new blood vessel development, we examined if they may contribute to adenosine-induced angiogenesis. We found that HMC-1 human mast cells express A2A, ...

Motor nerve terminals possess adenosine A(2A) receptors and brain derived neurotrophic factor (BDNF) TrkB receptors. In the present work we evaluated how BDNF actions on neuromuscular transmission would be influenced by adenosine ...

We previously reported that adenosine, through A(2A) receptor activation, potentiates synaptic actions of brain-derived neurotrophic factor (BDNF) in the hippocampus of infant (3-4 weeks) rats. Since A(2A)-receptor-mediated actions are more evident in ...

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)) ...

The physiological meaning of the coexpression of adenosine A2A receptors and group I metabotropic glutamate receptors in ?- aminobutyric acid (GABA)ergic striatal neurons is intriguing. Here we provide in vitro and in vivo evidence for a synergism between adenosine and ...

To ascertain the presence of adenosine receptors in the trout testis, cells isolated from testes at different spermatogenetic stages were cultured in the presence or absence of adenosine, adenosine receptor agonists, or antagonists and of cAMP analogs, for up to 20 min, or 20 hr, or 4.5 days. ...

Aims:? Adenosine plays an important role in the regulation of heart rate (HR) and vascular reactivity. However, the mechanisms underlying the acute effect of adenosine on arterial blood pressure in conscious mice are unclear. Therefore, this study investigated the effect of the nucleoside on mean arterial blood pressure (MAP) and HR in conscious mice. ...

Cell death caused by the accumulation of extracellular adenosine is believed to contribute to the profound loss of T lymphocytes in patients with severe combined immunodeficiency disease due to adenosine deaminase deficiency. Although adenosine is known to trigger apoptosis in thymocytes and peripheral T cells, the molecular basis of ...

The effects of nicorandil on systemic blood pressure (SBP) and heart rate (HR) responses to adenosine were compared with those to N6-cyclopentyladenosine (CPA), a selective adenosine A1 receptor agonist, and 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), a selective adenosine ...

Clinical studies implicate adenosine acting on esophageal nociceptive pathways in the pathogenesis of noncardiac chest pain originating from the esophagus. However, the effect of adenosine on esophageal afferent nerve subtypes is incompletely understood. We addressed the hypothesis that adenosine selectively activates esophageal ...

The adenosine A(2A) receptor in the basal ganglia is involved in the control of movement and plays a role in movement disorders such as Parkinsonism. Developing ligands to evaluate that receptor by noninvasive methods such as positron emission tomography has a high priority. In vitro ...

This study tested the hypothesis that adenosine, in murine corpora cavernosa, produces direct relaxation of smooth muscle cells and inhibition of contractile responses mediated by sympathetic nerve stimulation. Penes were excised from anesthetized male C57BL/6 mice, dissected, and cavernosal strips were mounted to record isometric force. Adenosine, ...

Prior studies demonstrate that adenosine, acting at one or more of its receptors, mediates the anti-inflammatory effects of methotrexate in animal models of both acute and chronic inflammation. Both adenosine A2A and A3 receptors contribute to the anti-inflammatory effects ...

A new series of 2,6,9-trisubstituted adenines (5-14) have been prepared and evaluated in radioligand binding studies for their affinity at the human A(1), A(2A) and A(3) adenosine receptors and in adenylyl cyclase experiments for their potency at the human A(2B) subtype. ...

Adenosine is a ubiquitous signaling molecule whose physiological functions are mediated by its interaction with four G-protein-coupled receptor subtypes, termed A(1), A(2A), A(2B) and A(3). As a result of increased metabolic rates, this nucleoside is released from a variety ...

Adenosine plays a dual role on acetylcholine (ACh) release from myenteric motoneurons via the activation of high-affinity inhibitory A(1) and facilitatory A(2A) receptors. The therapeutic potential of adenosine-related compounds for controlling intestinal motility and inflammation, prompted us ...

Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. ...

1. Changes in intracellular levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) were studied in rat isolated glomeruli and cultured glomerular mesangial cells exposed to adenosine and to the preferential A1 receptor agonist N6-R-1-methyl-2-phenylethyl adenosine (R-PIA), or the potent ...

Several recent studies suggest functional and molecular interactions between striatal adenosine A(2A) and cannabinoid CB(1) receptors. Here, we demonstrate that A(2A) receptors selectively modulate reinforcing effects of cannabinoids. We studied effects of A(2A) receptor ...

,6-dione Abbreviated name: [11 C]KW-6002 Synonym: Agent Category: Compound Target: Adenosine A2A receptorChem. Background [PubMed] Adenosine is an endogenous nucleoside that modulates a number of physiological functions receptors mediate stimulation. Changes in the ...

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. ...

The present work describes the synthesis of a pyrazinopurinedione derivative which was together with a series of pyrimidopurinedione derivatives tested for potential antiparkinsonian activity in two tests: the "oxotremorine" and the "reserpine" test. For the studies compounds which had shown affinity for the adenosine A(2A) ...

Methylxanthines, such as theophylline, have been used to treat cardiorespiratory disorders, whereas caffeine is the most widely consumed psychoactive agent in various soft drinks. Because of the worldwide use of these drugs and the recently synthesized xanthine derivatives, an intensive research on the cardiac actions of these substances is under progress. This review focuses on the molecular ...

Adenosine receptors have been implicated as important mediators of a diversity of physiological processes throughout the body. These receptors are members of the G protein-coupled receptor superfamily, a class of cell-surface receptors that, when activated, couple to a heterotrimeric G protein ...

Adenosine receptors are G protein-coupled receptors (GPCRs) that mediate the physiological functions of adenosine. In the central nervous system adenosine A2A receptors (A2ARs) are highly ...

Antagonism of the adenosine A(2a) receptor offers great promise in the treatment of Parkinson's disease. In the course of exploring pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A(2A) antagonists, which led to clinical candidate SCH 420814, we prepared ...

Adenosine has been implicated in suppressing the proinflammatory responses of classically activated macrophages induced by Th1 cytokines. Alternative macrophage activation is induced by the Th2 cytokines interleukin (IL)-4 and IL-13; however, the role of adenosine in governing alternative macrophage activation is unknown. We show here that ...

Two strains of inbred mice, CBA/J and SWR/J, have been identified which are, respectively, sensitive and insensitive to the behavioral and toxic effects of methylxanthines. Autoradiographic analyses of brain adenosine receptors were conducted with (/sup 3/H)CHA to label adenosine A-1 receptors and (/sup 3/H)NECA, ...

Exposure to cocaine during the fetal period can produce significant lasting changes in the structure and function of the brain. Cocaine exerts its effects on the developing brain by blocking monoamine transporters and impairing monoamine receptor signaling. Dopamine is a major central target of cocaine. In a mouse model, we show that cocaine exposure from embryonic day 8 (E8) ...

Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A(2A) receptors (A(2A)Rs) in the brain, but the specific neurons on which caffeine acts to ...

BACKGROUND: Adenosine has been shown to inhibit cell growth and induce apoptosis in the several cancer cells via intrinsic and extrinsic pathway. The present study was designed to understand the mechanism underlying adenosine-induced apoptosis in the DU-145, PC3, and LNcap-FGC10 human prostate cancer cells. METHODS: To observe cell viability and ...

The mechanisms responsible for vascular autoregulation in the brain during changes in mean arterial blood pressure are ambiguous. Potentially, adenosine, a purine nucleoside and potent vasodilator, may be involved as earlier studies have documented an increase in brain adenosine concentrations with cerebral ischemia and hypotension. Consequently, we tested ...

The effects of a novel purine derivative, N6-[2-(4-chlorophenyl)-bicyclo-2.2.2.octyl-(3)]-adenosine (EMD 28422), that has been found to influence central benzodiazepine receptors, has been compared to those of other adenosine analogues such as L-phenylisopropyladenosine (L-PIA), cyclohexyladenosine (CHA) and ...

Several selective antagonists for adenosine A(2A) receptors (A(2A)R) are currently under evaluation in clinical trials (phases I to III) to treat Parkinson's disease, and they will probably soon reach the market. The usefulness of these antagonists has been deduced from ...

To clarify if the behavioral interaction between ethanol and adenosine reported previously occur centrally or due to a peripheral hemodynamic change, the effect of i.c.v. adenosine agonists, N6-(R-phenylisopropyl)adenosine (R-PIA), N6-(S-phenylisopropyl)adenosine, 5'-(N-cyclopropyl)-carboxamidoadenosine, ...