P2 receptor-mediated inhibition of dopamine release in rat neostriatum

Axon terminal nucleotide P2 receptors mediating an inhibition of transmitter release have, so far, been detected in various sympathetically innervated tissues,(8,27) and on central noradrenergic,(14,26) glutamatergic(15) and serotonergic neurons. (28) We have now investigated the effect of ATP and related nucleotides on the release of endogenous dopamine from slices of rat neostriatum using fast cyclic voltammetry. Mutual interactions between the two neurotransmitters have been observed previously: ATP and related nucleotides induce a release of dopamine in PC12 pheochromocytoma cells, a frequently used model for sympathetic neurons;(10,22) they also increase the dopamine concentration in rat brain measured by in vivo microdialysis(16,32) and stimulate the uptake of dopamine by rat striatal synaptosomes.(3) Dopamine, in contrast, facilitates activation of ligand-gated cation channels (i. e. P2X(2) receptors) by ATP.(11,20) Here, we show that ATP and two of its analogues decrease the electrically evoked release of endogenous dopamine in rat neostriatum. The inhibitory effect of ATP is blocked by the P2 receptor antagonists suramin, reactive blue 2 and cibacron blue 3GA. Suramin, in addition, partly prevents the attenuation of dopamine release evoked by a single stimulus that follows a brief train of high-frequency pulses.These findings suggest the existence of release-inhibiting P2 receptors on dopaminergic nerve terminals and indicate that dopaminergic transmission in rat neostriatum might be modulated by an endogenous P2 receptor ligand, presumably ATP.