title: Isoflurane inhibits nicotinic acetylcholine receptor-mediated 22Na+ influx and muscarinic receptor-evoked cyclic GMP production in cultured bovine adrenal medullary cells.
abstract: The effects of isoflurane on 22Na+ influx, 45Ca2+ influx, catecholamine secretion and cyclic GMP production induced by three kinds of secretagogue (nicotinic agonists, veratridine and a high concentration of K+) have been investigated using cultured bovine adrenal medullary cells. (1) Isoflurane (1-6%) inhibited catecholamine secretion stimulated by carbachol, nicotine and dimethyl-4-phenylpiperazinium in a concentration-dependent manner. Isoflurane suppressed carbachol-evoked 22Na+ influx and 45Ca2+ influx at concentrations similar to those which suppressed catecholamine secretion. The inhibition of catecholamine secretion by isoflurane was not overcome by increasing the concentration of carbachol. (2) The inhibitory effects of isoflurane on veratridine-induced 22Na+ influx, 45Ca2+ influx and catecholamine secretion became evident when the concentration of isoflurane was raised to 4-6%, i.e. 2-3 fold higher than the concentrations (1-2%) employed clinically. (3) High K(+)-evoked 45Ca2+ influx and catecholamine secretion were not affected by isoflurane (1-6%). (4) Isoflurane (1-6%) attenuated the production of cyclic GMP caused by muscarine, but not that caused by atrial natriuretic peptide or by sodium nitroprusside. These results suggest that isoflurane, at clinical anesthetic concentrations, inhibits nicotinic acetylcholine receptor-mediated cell responses as well as muscarinic receptor-mediated cyclic GMP production in adrenal medullary cells.
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Minami
authors.forename: N
authors.initials: N
authors.lastname: Yanagihara
authors.forename: Y
authors.initials: Y
authors.lastname: Toyohira
authors.forename: M
authors.initials: M
authors.lastname: Tsutsui
authors.forename: A
authors.initials: A
authors.lastname: Shigematsu
authors.forename: A
authors.initials: A
authors.lastname: Wada
authors.forename: F
authors.initials: F
authors.lastname: Izumi
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology*; D009116:Muscarine / Q000494:pharmacology; D018727:Muscarinic Antagonists; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists; D009599:Nitroprusside / Q000494:pharmacology; D010622:Phencyclidine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects; D014701:Veratridine / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D002395:Catecholamines; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D015222:Sodium Channels; D009599:Nitroprusside; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D014701:Veratridine; D009116:Muscarine; D009320:Atrial Natriuretic Factor; D002217:Carbachol; D012964:Sodium; D007530:Isoflurane; D006152:Cyclic GMP; D010622:Phencyclidine; D011188:Potassium; D002118:Calcium