Ethanol-induced inhibition of carbachol-stimulated uptake of calcium in PC12 pheochromocytoma cells.
Using a rapid-quench technique the effects of ethanol on the uptake of 45Ca2+ into PC12 pheochromocytoma cells were studied in suspension. At concentrations achieved during acute intoxication in man (25-100 mM), ethanol inhibited both the carbachol-stimulated and K(+)-induced uptake of calcium. Inhibition of carbachol-stimulated uptake of Ca2+ occurred rapidly, within seconds at 27 degrees C, whereas inhibition of K(+)-induced uptake of Ca2+ developed more slowly. This disparity between the kinetics of these ethanol-induced inhibitions was unexpected, because the uptake of Ca2+, evoked by either stimulus, is thought to occur predominantly through a common pathway, namely voltage-sensitive Ca2+ channels. This difference may reflect differential effects of ethanol on multiple carbachol-activated pathways for entry of Ca2+. Alternatively, carbachol may facilitate the inhibitory action ethanol on voltage-dependent channels. This apparent facilitation was manifested principally by a more rapid onset of inhibition, although the extent of inhibition by ethanol, in the presence of carbachol, was also increased. In preincubation experiments, ethanol did not enhance the apparent agonist-induced desensitization of carbachol-evoked uptake of Ca2+. Nevertheless, an acute interaction between cholinergic agonists and ethanol, affecting homeostasis of Ca2+ may play a role in the pathophysiology of alcohol intoxication.
Koski
G
G
Department of Anesthesia, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Lawrence
K
K
Righi
D
D
D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002217:Carbachol / Q000037:antagonists & inhibitors*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010673:Pheochromocytoma / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D000431:Ethanol; D002217:Carbachol; D011188:Potassium; D002118:Calcium