Pharmacology of nicotine-induced increase in cytosolic Ca2+ concentrations in chick embryo ciliary ganglion cells.
Chick embryo ciliary ganglion cells were acutely isolated, and the mechanism(s) underlying the increase in the cytosolic Ca2+ concentration ([Ca]in) induced by high concentrations of nicotine examined using fura-2 microfluorometry. The order of potencies of nicotinic receptor agonists in increasing [Ca]in was ACh > nicotine = dimethylphenylpiperazinium > cytisine. The nicotine-induced increase in [Ca]in was inhibited not only by nicotinic antagonists but also by muscarinic antagonists, while the muscarine-induced [Ca]in increase was little affected by nicotinic antagonists. The nicotine-induced [Ca]in increase was inhibited by both L- and N-type Ca2+ channel blockers and potentiated by an L-type Ca2+ channel agonist, Bay-K-8644. Nicotine also increased the cytosolic Na+ concentration ([Na]in) as measured by sodium binding benzofuranisophthalate microfluorometry, and this [Na]in increase was inhibited by various agents which reportedly affected nicotinic receptor channels in adrenal chromaffin cells. These results suggest that nicotine increased Na+ influx through nicotinic receptor channels resulting in membrane depolarization, which in turn increased Ca2+ influx through voltage-dependent Ca2+ channels. However, nicotine still increased influxes of Ca2+ and Mn2+ in the absence of external Na+, suggesting that nicotinic receptor channels in these cells are permeable not only to monovalent cations but also to Ca2+ and Mn2+.
Sorimachi
M
M
Department of Physiology, Kagoshima University School of Medicine, Japan.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000378:metabolism; D002118:Calcium / Q000032:analysis* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002642:Chick Embryo; D003592:Cytophotometry; D016257:Fura-2; D005711:Gallopamil / Q000494:pharmacology; D005726:Ganglia, Parasympathetic / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D005711:Gallopamil; D008345:Manganese; D009538:Nicotine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001285:Atropine; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2