Modulation of nicotine-evoked [3H]dopamine release from rat striatal synaptosomes by voltage-sensitive calcium channel ligands.
The calcium channel subtypes mediating nicotine-evoked [3H]dopamine release from rat striatal synaptosomes were probed with L-, N-, and P-type calcium channel ligands. Responses to nicotine were blocked by the peptides omega-conotoxin GVIA and omega-agatoxin IVA. The affinity constants for these compounds were consistent with their actions at N- and P-type channels, respectively. Together, these channels mediate at least 90% of the calcium-dependent response to nicotine. The L-type antagonists nifedipine, verapamil, and nicardipine were also effective blockers of nicotine-evoked release with maximal effects of 80-100% inhibition. However, these effects occurred at concentrations 2-3 orders of magnitude higher than those necessary to block L-type channels. Moreover, Bay K8644, an L-type agonist, also blocked nicotine-evoked release. Together, these findings argue strongly against the involvement of L-type channels.
Prince
R J
RJ
Integrated Toxicology Program, Duke University Medical Center, Durham, NC 27710, USA.
Fernandes
K G
KG
Gregory
J C
JC
Martyn
I D
ID
Lippiello
P M
PM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects*
D015220:Calcium Channels; D009538:Nicotine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004492:Edetic Acid; D004298:Dopamine