Effects of adenosine A1 and A2 receptor activation on electrically evoked dopamine and acetylcholine release from rat...

The authors investigated how electrically evoked [3H]dopamine (DA) and [14C]acetylcholine (ACh) release in the rat striatum is affected, directly or indirectly, by adenosine A1 and A2A receptor activation. Striatal slices, preincubated with [3H]DA and [14C] choline, were superfused continuously and subjected to electrical field stimulation. The electrically evoked release of both [3H] and [14C] was tetrodotoxin sensitive and calcium dependent. The release of both labels was augmented by haloperidol and sulpiride but only the [14C]ACh release was increased by 7-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol (each at 1 microM). The A1 receptor-selective agonist cyclohexyladenosine and the A2A receptor-selective agonist 2-[4-(2-carboxymethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS 21680) both caused a concentration-dependent (range, 0.01-1 microM) inhibition of electrically evoked DA and ACh release and with a surprisingly similar potency. The potency of both compounds, and particularly of cyclohexyladenosine, increased when they were allowed to equilibrate for a longer period with the slices. The effect of both compounds was blocked by the A1-selective antagonist 1,3-dipropyl-8-cyclopentyl xanthine (0.1 microM). CGS 21680 never caused any stimulation of DA or ACh release. The ability of the D2 agonist quinpirole to inhibit ACh release was reduced by CGS 21680 in the presence or absence of 0.1 microM 1,3-dipropyl-8-cyclopentyl xanthine. CGS 21680 did not alter the D2 receptor inhibition of DA release. In summary, adenosine analogs inhibit DA and ACh release from rat striatum by a receptor that may be different from those hitherto characterized.(ABSTRACT TRUNCATED AT 250 WORDS)