ISOFLURANE INHIBITS NICOTINIC ACETYLCHOLINE RECEPTOR-MEDIATED NA-22(-EVOKED CYCLIC-GMP PRODUCTION IN CULTURED BOVINE ADRENAL-MEDULLARY CELLS() INFLUX AND MUSCARINIC RECEPTOR)

The effects of isoflurane on Na-22(+) influx, Ca-45(2+) influx, catech olamine 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 stimul ated by carbachol, nicotine and dimethyl-4-phenylpiperazinium in a con centration-dependent manner. Isoflurane suppressed carbachol-evoked Na -22(+) influx and Ca-45(2+) influx at concentrations similar to those which suppressed catecholamine secretion. The inhibition of catecholam ine secretion by isoflurane was not overcome by increasing the concent ration of carbachol. (2) The inhibitory effects of isoflurane on verat ridine-induced Na-22(+) influx, Ca-45(2+) influx and catecholamine sec retion 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 Ca-45(2+) influx and catecholamine secr etion were not affected by isoflurane (1-6%). (4) Isoflurane (1-6%) at tenuated the production of cyclic GMP caused by muscarine, but not tha t caused by atrial natriuretic peptide or by sodium nitroprusside. The se results suggest that isoflurane, at clinical anesthetic concentrati ons, inhibits nicotinic acetylcholine receptor-mediated cell responses as well as muscarinic receptor-mediated cyclic GMP production in adre nal medullary cells.