ADENOSINE A(2A) RECEPTOR-MEDIATED MODULATION OF STRIATAL [H-3] GABA AND [H-3] ACETYLCHOLINE-RELEASE

The ability of adenosine agonists to modulate K+-evoked gamma-[H-3]ami nobutyric acid ([H-3]GABA) and acetylcholine (ACh) release from rat st riatal synaptosomes was investigated. The A(2a) receptor-selective ago nist CGS 21680 inhibited Ca2+-dependent [H-3]GABA release evoked by 15 mM KCl with a maximal inhibition of 29 +/- 4% (IC50 of similar to 4 x 10(-12) M). The relative order of potency of three agonists was CGS 2 1680 greater than or equal to B-N-ethylcarboxamidoadenosine > R-phenyl isopropyladenosine (R-PIA), with the inhibition being blocked by A(2a) receptor-selective antagonists (CP 66,713 and CGS 15943A) but not by the A(1)-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCP X). When release of [H-3]GABA was evoked by 30 mM KCl, no significant inhibition was observed. In contrast, CGS 21680 stimulated the release of [H-3]ACh evoked by 30 mM KCl, with a maximal stimulation of 26 +/- 5% (IC50 of similar to 10(-11) M). This effect was blocked by CP 66,7 13 but not by DPCPX. The A(1) agonist R-PIA inhibited [H-3]ACh release , an effect blocked by DPCPX. It is concluded that adenosine A(2a) rec eptors are present on both GABAergic and cholinergic striatal nerve te rminals where they inhibit and stimulate transmitter release, respecti vely.