Binding of [3H]phencyclidine to adrenal medullary cells: inhibition of 22Na influx, 45Ca influx, 86Rb efflux and catecholamine secretion caused by carbachol and veratridine.
In bovine adrenal medullary cells, phencyclidine inhibited carbachol-induced influx of 22Na, 45Ca and secretion of catecholamines in a concentration-dependent manner with a similar potency (IC50 7.0 microM). Phencyclidine also suppressed veratridine-induced influx of 22Na, 45Ca and secretion of catecholamines (IC50 60.0 microM). High K-induced 45Ca influx and catecholamine secretion were not affected by phencyclidine. In the cells preloaded with 86Rb (an alternative tracer for 42K), phencyclidine inhibited the efflux of 86Rb caused by carbachol (IC50 10.0 microM) or by veratridine (IC50 56.0 microM), but had no effect on high K-induced 86Rb efflux. [3H]Phencyclidine bound specifically to adrenal medullary cells, and binding was saturable, reversible and with two different equilibrium dissociation constants (4.3 and 77.4 microM). In a competition experiment, the specific binding of [3H]phencyclidine was not inhibited by carbachol, muscarine, D-tubocurarine, hexamethonium, tetrodotoxin, veratridine and scorpion venom. The present findings suggest: (1) phencyclidine does not inhibit voltage-dependent Ca channels and Ca-dependent K channels; (2) phencyclidine binds to two populations of sites, each of which is functionally linked to nicotinic receptor-ion channel complex and to voltage-dependent Na channels, and inhibits Na influx caused by carbachol and veratridine. Inhibition of Na influx by phencyclidine leads to the reduction of Ca influx, K efflux and catecholamine secretion caused by carbachol and veratridine.
Wada
A
A
Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Arita
M
M
Yanagihara
N
N
Izumi
F
F
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D007700:Kinetics; D010622:Phencyclidine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
D002395:Catecholamines; D014701:Veratridine; D002217:Carbachol; D012964:Sodium; D014702:Veratrine; D010622:Phencyclidine; D012413:Rubidium; D011188:Potassium; D002118:Calcium