title: Adenosine receptor-mediated modulation of acetylcholine release from rat striatal synaptosomes.
abstract: 1. The effects of A1 and A2a adenosine receptor agonists on the veratridine-evoked release of [3H]-acetylcholine ([3H]-ACh) from rat striatal synaptosomes was investigated by use of the A1-selective agonist, R-PIA and the 185 fold selective A2a agonist, CGS 21680. The effects of NECA, which is equipotent at both receptor subtypes, were also studied. 2. The evoked release of [3H]-ACh was significantly enhanced by the A2a agonist CGS 21680 but decreased by the A1 agonist, R-PIA. The effects of NECA were dependent on the concentration used, with high concentrations inhibiting and low concentrations enhancing the evoked release of [3H]-ACh. In the absence of any antagonists, the rank order of potency for these three drugs on increasing [3H]-ACh release was CGS 21680 > NECA > R-PIA. 3. The stimulatory effects of CGS 21680 and low NECA concentrations on evoked [3H]-ACh release were antagonized by the A2a receptor antagonists, CP66,713 (300 nM) and CGS 15943A (50 nM) whilst the inhibitory effects of R-PIA were reversed by the selective A1 antagonist, DPCPX (4 nM). In the presence of DPCPX, NECA greatly enhanced the evoked release of [3H]-ACh at all concentrations studied when, during such A1 receptor blockade, the rank order of potency was NECA >> CGS 21680 > R-PIA. 4. These results demonstrate that both A1 and A2a adenosine receptors modulate the veratridine-evoked release of [3H]-ACh from rat striatal synaptosomes.
authors.affiliation: Department of Pharmacology, University of Cambridge.
authors.forename: K A
authors.initials: KA
authors.lastname: Kirkpatrick
authors.forename: P J
authors.initials: PJ
authors.lastname: Richardson
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D003342:Corpus Striatum / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D010627:Phenethylamines / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000145:classification / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism*; D014316:Tritium; D014701:Veratridine / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D010627:Phenethylamines; D058915:Purinergic P1 Receptor Antagonists; D011719:Pyrazines; D018047:Receptors, Purinergic P1; D014970:Xanthines; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D014701:Veratridine; C072107:CP 66713; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D000109:Acetylcholine