Adenosine A2a Receptor‐Mediated Modulation of Striatal [3H]GABA and [3H]Acetylcholine Release

Abstract: The ability of adenosine agonists to modulate K+‐evoked 4D†‐[3H]aminobutyric acid ([3H]GABA) and acetylcholine (ACh) release from rat striatal synaptosomes was investigated. The A2a receptor‐selective agonist CGS 21680 inhibited Ca2+‐dependent [3H]GABA release evoked by 15 mM KCI with a maximal inhibition of 29 ± 4% (IC50 of ∼4 ± 10 −12M). The relative order of potency of three agonists was CGS 21680 ± 5′‐N‐ethylcarboxamidoadenosine > R‐phenylisopropyladenosine (R‐PIA), with the inhibition being blocked by A2a receptor‐selective antagonists (CP 66,713 and CGS 15943A) but not by the A1‐selective antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX). When release of [3H]GABA was evoked by 30 mM KCI, no significant inhibition was observed. In contrast, CGS 21680 stimulated the release of [3H]ACh evoked by 30 mM KCI, with a maximal stimulation of 26 ± 5% (IC50 of ∼10−11M). This effect was blocked by CP 66,713 but not by DPCPX. The A1 agonist R‐PIA inhibited [3H]ACh release, an effect blocked by DPCPX. It is concluded that adenosine A2a receptors are present on both GABAergic and cholinergic striatal nerve terminals where they inhibit and stimulate transmitter release, respectively. Key Words: GABA—Acetylcholine—Adenosine receptors—Striatum.

[1]  T. Palmer,et al.  Adenosine receptors , 1995, Neuropharmacology.

[2]  T J Furlong,et al.  Molecular characterization of a human brain adenosine A2 receptor. , 1992, Brain research. Molecular brain research.

[3]  J. Phillis,et al.  Excitatory Transmitter Amino Acid Release from the Ischemic Rat Cerebral Cortex: Effects of Adenosine Receptor Agonists and Antagonists , 1992, Journal of neurochemistry.

[4]  J. Ribeiro,et al.  Evidence for the presence of excitatory A2 adenosine receptors in the rat hippocampus , 1992, Neuroscience Letters.

[5]  J. Phillis,et al.  The selective A2 adenosine receptor agonist CGS 21680 enhances excitatory transmitter amino acid release from the ischemic rat cerebral cortex , 1992, Neuroscience Letters.

[6]  S. Rivkees,et al.  Molecular cloning and expression of the cDNA for a novel A2-adenosine receptor subtype. , 1992, Molecular endocrinology.

[7]  J. Xuereb,et al.  Adenosine receptors in post‐mortem human brain , 1992, British journal of pharmacology.

[8]  J. Palacios,et al.  Adenosine A2 receptors: Selective localization in the human basal ganglia and alterations with disease , 1991, Neuroscience.

[9]  K. Jacobson,et al.  Distinct pathways of desensitization of A1- and A2-adenosine receptors in DDT1 MF-2 cells. , 1991, Molecular pharmacology.

[10]  S. Schiffmann,et al.  Striatal Restricted Adenosine A2 Receptor (RDC8) Is Expressed by Enkephalin but Not by Substance P Neurons: An In Situ Hybridization Histochemistry Study , 1991, Journal of neurochemistry.

[11]  C. Hammond,et al.  μ-Opioid-receptor-mediated inhibidon of the N-type calcium-channel current , 1991, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[12]  J. Phillis,et al.  Subtypes of adenosine receptors in the brainstem mediate opposite blood pressure responses , 1991, Neuropharmacology.

[13]  R. G. Browne,et al.  4‐Amino(1,2,4)triazolo(4,3‐a)quinoxalines. A Novel Class of Potent Adenosine Receptor Antagonists and Potential Rapid‐Onset Antidepressants. , 1991 .

[14]  J. Phillis,et al.  Characterization of the depression of rat cerebral cortical neurons by selective adenosine agonists , 1991, Brain Research.

[15]  S Schiffmann,et al.  RDC8 codes for an adenosine A2 receptor with physiological constitutive activity. , 1990, Biochemical and biophysical research communications.

[16]  S. Cohen,et al.  Distinct Muscarinic Receptor Subtypes Differentially Modulate Acetylcholine Release from Corticocerebral Synaptosomes , 1990, Journal of neurochemistry.

[17]  M. Reddington,et al.  Both A1 and A2a Purine Receptors Regulate Striatal Acetylcholine Release , 1990, Journal of neurochemistry.

[18]  T. Dunwiddie,et al.  Effects of the selective adenosine A2 receptor agonist CGS 21680 on in vitro electrophysiology, cAMP formation and dopamine release in rat hippocampus and striatum. , 1990, The Journal of pharmacology and experimental therapeutics.

[19]  M. Williams,et al.  [3H]CGS 21680, a selective A2 adenosine receptor agonist directly labels A2 receptors in rat brain. , 1989, The Journal of pharmacology and experimental therapeutics.

[20]  M. Verhage,et al.  Ca2+‐Dependent Regulation of Presynaptic Stimulus‐Secretion Coupling , 1989, Journal of neurochemistry.

[21]  M. Williams,et al.  Direct autoradiographic localization of adenosine A2 receptors in the rat brain using the A2-selective agonist, [3H]CGS 21680. , 1989, European journal of pharmacology.

[22]  M. Raiteri,et al.  Release‐regulating autoreceptors of the GABAB‐type in human cerebral cortex , 1989, British journal of pharmacology.

[23]  J. Nadler,et al.  Regulation of Glutamate and Aspartate Release from Slices of the Hippocampal CA1 Area: Effects of Adenosine and Baclofen , 1988, Journal of neurochemistry.

[24]  C. Gerfen,et al.  Distribution of striatonigral and striatopallidal peptidergic neurons in both patch and matrix compartments: an in situ hybridization histochemistry and fluorescent retrograde tracing study , 1988, Brain Research.

[25]  D. Nicholls,et al.  4‐Aminobutyrate Can Be Released Exocytotically from Guinea‐Pig Cerebral Cortical Synaptosomes , 1987, Journal of neurochemistry.

[26]  G. Ghai,et al.  Biochemical characterization of the triazoloquinazoline, CGS 15943, a novel, non-xanthine adenosine antagonist. , 1987, The Journal of pharmacology and experimental therapeutics.

[27]  K. Starke,et al.  A Search for Receptors Modulating the Release of γ‐[3H]Aminobutyric Acid in Rabbit Caudate Nucleus Slices , 1986, Journal of neurochemistry.

[28]  A. Dolphin,et al.  An adenosine agonist inhibits and a cyclic AMP analogue enhances the release of glutamate but not GABA from slices of rat dentate gyrus , 1983, Neuroscience Letters.

[29]  T. Stone.  Purine receptors involved in the depression of neuronal firing in cerebral cortex , 1982, Brain Research.

[30]  J. Phillis.  Evidence for an A2‐like adenosine receptor on cerebral cortical neurons , 1982, The Journal of pharmacy and pharmacology.

[31]  D. Nicholls,et al.  Calcium-ion transport by intact synaptosomes. Intrasynaptosomal compartmentation and the role of the mitochondrial membrane potential. , 1980, The Biochemical journal.

[32]  T. Stone,et al.  ADENOSINE INHIBITION OF γ‐AMINOBUTYRIC ACID RELEASE FROM SLICES OF RAT CEREBRAL CORTEX , 1980 .

[33]  Margarete Müller,et al.  ADENOSINE REGULATES VIA TWO DIFFERENT TYPES OF RECEPTORS, THE ACCUMULATION OF CYCLIC AMP IN CULTURED BRAIN CELLS , 1979, Journal of neurochemistry.

[34]  N. Porter,et al.  Desensitization of adenosine and dopamine receptors in rat brain after treatment with adenosine analogs. , 1988, The Journal of pharmacology and experimental therapeutics.