ATP increases extracellular dopamine level through stimulation of P2Y purinoceptors in the rat striatum.

The effect of ATP on release of dopamine (DA) from rat striatum was studied using in vivo microdialysis. ATP increased the striatal extracellular levels of DA dose-dependently. These analogs produced an increase in DA according to this order of potency: 2-methylthio ATP > ATP > or = alpha,beta-methylene ATP > ADP > AMP > adenosine. Adenosine 5'-[beta, gamma imido]-triphosphate had a more prolonged effect on the increase in DA level than ATP. The ATP-induced increase in DA was inhibited by adding suramin, a nonselective P2 purinoceptor antagonist, and reactive blue 2, a P2Y purinoceptor antagonist, but not inhibited by xanthine amine congener, an adenosine receptor antagonist. Pertussis toxin reduced the increase in DA produced by ATP, which suggests that the P2 purinoceptor may be coupled with a G-protein in the rat striatum. Results suggest that P2Y purinoceptors may involve an ATP-induced increase in DA. The ATP-induced release of DA was tetrodotoxin-sensitive, Ca(2+)-dependent and was abolished by omega-conotoxin GVIA, indicating that the opening of voltage-sensitive Na+ channel and the Ca2+ influx through the N-type voltage-dependent calcium channel are both required for the ATP-induced increase in DA. The ATP-induced increase in DA is presumably due to the release of DA via the stimulation of P2Y purinoceptors in the rat striatum.