Adenosine A2a receptor-mediated modulation of striatal [3H]GABA and [3H]acetylcholine release.
The ability of adenosine agonists to modulate K(+)-evoked gamma-[3H]aminobutyric acid ([3H]GABA) and acetylcholine (ACh) release from rat striatal synaptosomes was investigated. The A2a receptor-selective agonist CGS 21680 inhibited Ca(2+)-dependent [3H]GABA release evoked by 15 mM KCl with a maximal inhibition of 29 +/- 4% (IC50 of approximately 4 x 10(-12) M). The relative order of potency of three agonists was CGS 21680 > or = 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 KCl, no significant inhibition was observed. In contrast, CGS 21680 stimulated the release of [3H]ACh evoked by 30 mM KCl, with a maximal stimulation of 26 +/- 5% (IC50 of approximately 10(-11) M). 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.
Kirk
I P
IP
Department of Pharmacology, University of Cambridge, England.
Richardson
P J
PJ
D000109:Acetylcholine / Q000378:metabolism*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D010627:Phenethylamines; D018047:Receptors, Purinergic P1; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D000109:Acetylcholine