title: Effects of L- and N-type Ca2+ channel antagonists on excitatory amino acid-evoked dopamine release.
abstract: In the present study we tested the effect of dihydropyridine (DHP) Ca2+ channel antagonists and of omega-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 microM) 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 microM) 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-induced [3H]DA release by micromolar concentrations of DHPs must be mediated by actions other than inhibition of L-type Ca2+ channels. omega-Conotoxin GVIA (3 microM) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Chaudieu
authors.forename: R
authors.initials: R
authors.lastname: Alonso
authors.forename: H
authors.initials: H
authors.lastname: Mount
authors.forename: R
authors.initials: R
authors.lastname: Quirion
authors.forename: P
authors.initials: P
authors.lastname: Boksa
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017459:Receptors, Amino Acid / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D010456:Peptides, Cyclic; D017459:Receptors, Amino Acid; D016202:N-Methylaspartate; D014701:Veratridine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D016318:Quisqualic Acid; D020866:omega-Conotoxin GVIA; D009568:Nitrendipine; D007608:Kainic Acid; D004298:Dopamine