title: Ketamine inhibits 45Ca influx and catecholamine secretion by inhibiting 22Na influx in cultured bovine adrenal medullary cells.
abstract: The effects of ketamine, an intravenous anesthetic, on 22Na influx, 45Ca influx and catecholamine secretion were investigated in cultured bovine adrenal medullary cells. Ketamine inhibited carbachol-induced 45Ca influx and catecholamine secretion in a concentration-dependent manner with a similar potency (IC50 40 microM). Ketamine also reduced veratridine-induced 45Ca influx and catecholamine secretion (IC50 260 microM) but did not affect high K-induced 45Ca influx and catecholamine secretion. The influx of 22Na caused by carbachol or by veratridine was suppressed by ketamine with a concentration-inhibition curve similar to that of 45Ca influx and catecholamine secretion. Inhibition by ketamine of the carbachol-induced influx of 22Na, 45Ca and secretion of catecholamines was not reversed by the increased concentrations of carbachol. These observations indicate that ketamine, at clinical concentrations, can inhibit nicotinic receptor-associated ionic channels and that the inhibition of Na influx via the receptor-associated ionic channels is responsible for the inhibition of carbachol-induced Ca influx and catecholamine secretion. At higher concentrations, the anesthetic also inhibits voltage-dependent Na channels but has no effect on voltage-dependent Ca channels.
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D012979:Sodium Radioisotopes; D014701:Veratridine / Q000494:pharmacology
chemical_list: D002132:Calcium Radioisotopes; D002395:Catecholamines; D007473:Ion Channels; D012979:Sodium Radioisotopes; D007649:Ketamine; D014701:Veratridine; D012964:Sodium; D002118:Calcium