Ethanol-induced inhibition of carbachol-stimulated uptake of calcium in PC12 pheochromocytoma cells

Abstract

Using a rapid-quench technique the effects of ethanol on the uptake of 45Ca 2+ 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 Ca 2+ occurred rapidly, within seconds at 27°C, whereas inhibition of K +-induced uptake of Ca 2+ developed more slowly. This disparity between the kinetics of these ethanol-induced inhibitions was unexpected, because the uptake of Ca 2+ evoked by either stimulus, is thought to occur predominantly through a common pathway, namely voltage-sensitive Ca 2+channels. This difference may reflect differential effects of ethanol on multiple carbachol-activated pathways for entry of Ca 2+. Alternatively, carbachol may facilitate the inhibitory action of 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 Ca 2+. Nevertheless, an acute interaction between cholinergic agonists and ethanol, affecting homeostasis of Ca 2+ may play a role in the pathophysiology of alcohol intoxication.