Functional modulation of human "ganglionic-like" neuronal nicotinic acetylcholine receptors (nAChRs) by L-type calcium channel antagonists.
Recent studies suggest that the neuronal nicotinic acetylcholine receptors present on chromaffin cells contain a 1,4-dihydropyridine-sensitive site whose occupation blocks membrane depolarization (1). In the present study, several L-type Ca2+ channel blockers inhibited the activation of the nAChRs present in the human neuroblastoma cell line, IMR 32, in a dose-dependent manner with IC50 values ranging from 0.8-3 microM. In contrast, omega-Conotoxin GVIA and omega-Agatoxin IVA had no effect up to 100 microM. Furthermore, the inorganic channel blocker, cadmium, had no effect either alone or on the modulatory role of the L-type antagonists, suggesting that the effects of these agents on nAChRs are not mediated via an interaction with calcium channels but possibly via a direct interaction with the nAChR ionophore.
Donnelly-Roberts
D L
DL
Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Arneric
S P
SP
Sullivan
J P
JP
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology; D006801:Humans; D017275:Isradipine / Q000494:pharmacology; D009447:Neuroblastoma; D009474:Neurons / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology*; D013111:Spider Venoms / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D011978:Receptors, Nicotinic; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D002104:Cadmium; D009553:Nimodipine; D009538:Nicotine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020866:omega-Conotoxin GVIA; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D017275:Isradipine