Abstract
In rat hepatocytes loaded with fluorescein isothiocyanate (FΙTC)-dextran, ethanol (100 mM) led to a biphasic increase of the pH of endocytotic vesicles (control pHves = 6.11 ± 0.06, n = 77) starting with a peak (ΔpHves = +0.15 ± 0.01) followed by a sustained plateau (ΔpHves = +0.09 ± 0.02). The alkalinizing effect of ethanol was fully reversible and was half-maximal at ethanol concentrations M. The effects of ethanol were mimicked by low concentrations (0.1 mM) of acetaldehyde, but not by acetate or a lactate-induced shift of the NADH/ NAD+ system to a more reduced state. Inhibition of alcohol dehydrogenase by 4-methylpyrazole (2 mM) abolished the effects of ethanol on pHves, but not those of acetaldehyde. The ethanol-induced pHves changes were largely abolished in the presence of colchicine, the chloride channel blocker 4,4/-diisothiocyanatostilbene-2,2’-disulfonic acid, pertussis and cholera toxin and the tyrosine kinase inhibitors erbstatin analogue and genistein. The results suggest that ethanol via acetaldehyde activates a signal transduction mechanism which triggers an alkalinization of pHves. This may contribute to the known effects of ethanol on the endocytotic pathway.
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