Inability of Ca2+ influx through nicotinic ACh receptor channels to stimulate catecholamine secretion in bovine adrenal chromaffin cells: studies with fura-2 and SBFI microfluorometry.
The concentration of cytosolic Ca2+ ([Ca]in) and catecholamine (CA) secretion were examined in bovine adrenal chromaffin cells to determine whether Ca2+ influx through nicotinic ACh receptor (nAChR) channels contributes to CA secretion induced by nAChR stimulation. Nicotine added under Na(+)-free conditions caused a marked increase in [Ca]in and quenching of fura-2 fluorescence in the presence of Mn2+, suggesting the stimulated entry of divalent cations through nAChR channels. However, nicotine-induced increase in CA secretion occurred only at a non-physiologically high external Ca2+ concentration under Na(+)-free conditions. Both the nicotine-induced increase in [Ca]in and CA secretion under Na(+)-free conditions were reduced in the presence of hexamethonium, methoxyverapamil (D600), nifedipine, Bay-K-8644, clonidine, and guanethidine. All of these agents inhibited the nicotine-induced increase in cytosolic Na+ concentration in a dose-dependent manner, as measured by SBFI microfluorometry. The present results suggest that Ca2+ influx through nAChR channels under physiological conditions may not contribute to CA secretion.
Sorimachi
M
M
Department of Physiology, Kagoshima University, School of Medicine, Japan.
Nishimura
S
S
Yamagami
K
K
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism*; D002413:Cations, Divalent; D002417:Cattle; D003000:Clonidine / Q000494:pharmacology; D003592:Cytophotometry; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D016257:Fura-2 / Q000737:chemistry; D005711:Gallopamil / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D008345:Manganese / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D015220:Calcium Channels; D002395:Catecholamines; D002413:Cations, Divalent; D011978:Receptors, Nicotinic; D005711:Gallopamil; D018738:Hexamethonium; D008345:Manganese; D010095:Oxotremorine; C042743:oxotremorine M; D009538:Nicotine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D012964:Sodium; D009543:Nifedipine; D003000:Clonidine; D002118:Calcium; D016257:Fura-2; D006145:Guanethidine