Effects of L- and N-type Ca channel antagonists on excitatory amino acid-evoked dopamine release |
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Authors: | Isabelle Chaudieu Richard Alonso Howard Mount Rmi Quirion Patricia Boksa |
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Institution: | Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Quebec, Canada |
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Abstract: | In thc present study we tested the effect of dihydropyridine (DHP) Ca2+ channel antagonists and of ω-conotoxin GVIA on 3H]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 Ca2+ channels in these EAA-mediated processes. Micromolar concentrations (10–30 μM) of DHP L-type Ca2+ channel antagonists inhibited 3H]DA release evoked by N-methyl-D-aspartate (NMDA), kainate, quisqualate or veratridine. 3H]DA release evoked by the L-type Ca2+ 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 3H]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 Ca2+ channels is able to evoke 3H]DA release. However activation of L-type channels is not involved in EAA-induced 3H]DA release and therefore inhibition of EAA-induccd 3H]DA release by micromolar concentrations of DHPs must be mediated by actions other than inhibition of L-type Ca2+ channels. ω-Conotoxin GVIA (3 μM) had no effect on 3H]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 3H]DA release evoked by NMDA or kainate, suggesting that N-type Ca2+ channels could possibly play a role in FAA-mediated responses in these cells. |
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Keywords: | Ca2+ channels Dihydropyridines NMDA (N-methyl-D-aspartate) Excitatory amino acid Dopamine Transmitter release Mesencephalon |
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