Effects of L- and N-type Ca2+ channel antagonists on excitatory amino acid-evoked dopamine release.

Abstract In thc present study we tested the effect of dihydropyridine (DHP) Ca 2+ channel antagonists and of ω-conotoxin GVIA on [ 3 H]dopamine (DA) release evoked by the activation of excitatory amino acid (EAA) receptors in cultures of fetal rat ventral mesencephalon, in order to investigate the role of voltage-sensitive L- and N-type Ca 2+ channels in these EAA-mediated processes. Micromolar concentrations (10–30 μM) of DHP L-type Ca 2+ channel antagonists inhibited [ 3 H]DA release evoked by N-methyl-D-aspartate (NMDA), kainate, quisqualate or veratridine. [ 3 H]DA release evoked by the L-type Ca 2+ channel agonist, Bay K 8644, was inhibited by lower concentrations (0.1–1 μM) of the DHP antagonist, nitrendipine, than was the release evoked by EAAs. The DHP antagonist, ( + )-PN 200-110, was more potent than ( − )-PN 200-110 in inhibiting [ 3 H]DA release evoked by Bay K 8644, but the two stereoisomers were equipotent in inhibiting NMDA-evoked release. These results indicate that activation of L-type Ca 2+ channels is able to evoke [ 3 H]DA release. However activation of L-type channels is not involved in EAA-induced [ 3 H]DA release and therefore inhibition of EAA-induccd [ 3 H]DA release by micromolar concentrations of DHPs must be mediated by actions other than inhibition of L-type Ca 2+ channels. ω-Conotoxin GVIA (3 μM) had no effect on [ 3 H]DA release evoked by Bay K 8644, indicating that the toxin may selectively inhibit N-type channels in this preparation. ω-Conotoxin GVIA (3 μM) partially inhibited [ 3 H]DA release evoked by NMDA or kainate, suggesting that N-type Ca 2+ channels could possibly play a role in FAA-mediated responses in these cells.