title: Investigations of the roles of dihydropyridine and omega-conotoxin-sensitive calcium channels in mediating depolarisation-evoked endogenous dopamine release from striatal slices.
abstract: The relative roles of L- and N-type voltage-sensitive calcium channels (VSCC) in mediating endogenous dopamine release have been investigated by examining the effects of the dihydropyridine (DHP) agonist BAY K 8644 and the antagonist PN 200-110, as well as the VSCC-blocking peptide omega-conotoxin GVIA, on depolarisation-evoked dopamine release from superfused rat striatal slices. Dopamine release evoked by electrical field stimulation was virtually unaffected by either of the DHP drugs, but release evoked by raising the K+ concentration to 25 mmol/l was significantly increased by BAY K 8644 and reduced stereospecifically by PN 200-110. Quantitative differences between electrically-evoked and K+-evoked dopamine release with respect to their dependence on extracellular calcium concentration were also observed, with electrically-evoked release requiring higher calcium concentrations. The adenylate cyclase activator forskolin itself increased dopamine release, but did not appear to influence the effectiveness of either DHP drug in altering dopamine release. In contrast to the relatively small effects of the DHP drugs, omega-conotoxin produced a major reduction in electrically-evoked dopamine release as well as a substantial decrease in K+-evoked release. Since omega-conotoxin is thought to block both L- and N-type neuronal VSCC whereas DHP drugs affect only L-type VSCC, these findings suggest that electrically-evoked dopamine release is mediated mainly by calcium influx through N-type VSCC, accounting for the reported lack of effect of many organic calcium antagonists on this process. In contrast, K+-evoked dopamine release appears to involve both L- and N-type VSCC, and can occur at lower extracellular calcium concentrations.
authors.affiliation: Department of Pharmacology, University of Leeds, UK.
authors.forename: H
authors.initials: H
authors.lastname: Herdon
authors.forename: S R
authors.initials: SR
authors.lastname: Nahorski
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D008978:Mollusk Venoms; D009467:Neuromuscular Depolarizing Agents; D011954:Receptors, Dopamine; D005576:Colforsin; D020866:omega-Conotoxin GVIA; D011188:Potassium; D002118:Calcium; D004298:Dopamine