Adenosine receptor‐mediated modulation of acetylcholine release from rat striatal synaptosomes

Abstract

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. 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. 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. These results demonstrate that both A1 and A2a adenosine receptors modulate the veratridine‐evoked release of [3H]‐ACh from rat striatal synaptosomes. 1993 British Pharmacological Society