Mechanism of the differential effects of halothane on nicotinic- and muscarinic-receptor-mediated responses of the dog adrenal medulla.
The mechanism of the differential effects of halothane on the cholinergic nicotinic and muscarinic responses of adrenal medullary cells was studied using isolated dog adrenals perfused with modified Locke's solution. The concentrations of halothane exhibiting 50% inhibition of catecholamine release induced by nearly equipotent agonists were 0.8% for nicotine, 1.9% for acetylcholine, and 2.8% for muscarine, respectively. Per cent inhibition by halothane (1.5%) of nicotine-induced catecholamine release was 98.5%, and those of veratridine-, acetylcholine-, CaCl2-, Na+-deprivation- and muscarine-induced catecholamine release were 89.7, 32.5, 21.4, 10.1, and 9.5%, respectively. Halothane showed an inhibitory effect on the agonist-induced catecholamine release in Na+-free solution to the same extent as in Na+-containing solution. Tetrodotoxin abolished veratridine-induced catecholamine release completely and decreased nicotine-induced release slightly, whereas it had no effect on either muscarine- or acetylcholine-induced catecholamine release. Verapamil inhibited acetylcholine-induced catecholamine release by 65%, and nicotine- and muscarine-induced release by 79% and 26%, respectively. The results suggest that halothane at clinical concentrations selectively inhibits the nicotinic-receptor-mediated responses of the dog adrenal medulla. The mechanism involved might be the susceptibility to halothane of the Ca++ channels that are linked to the respective nicotinic and muscarinic receptors. An inhibition of exocytosis might be also indicated as part of the effect of halothane.
D000109:Acetylcholine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004285:Dogs; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D009116:Muscarine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*
D002395:Catecholamines; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D009538:Nicotine; D009116:Muscarine; D000109:Acetylcholine; D006221:Halothane