PMID: 8587652Aug 1, 1995Paper

Ethanol inhibits muscarinic receptor-stimulated phosphoinositide metabolism and calcium mobilization in rat primary cortical cultures

Neurochemical Research
K A KovacsL G Costa

Abstract

In recent years, it has been hypothesized that muscarinic receptor-stimulated phosphoinositide (PI) metabolism may represent a relevant target for the developmental neurotoxicity of ethanol. Age-, brain region-, and receptor-specific inhibitory effects of ethanol on this system have been found, both in vitro and after in vivo administration. As a direct consequence of this action, alterations of calcium homeostasis would be expected, through alterations of inositol trisphosphate formation, which mediates intracellular calcium mobilization. In the present study, the effects of ethanol (50-500 mM) on carbachol-stimulated PI metabolism and free intracellular calcium levels were investigated in rat primary cortical cultures, by measuring release of inositol phosphates and utilizing the two calcium probes fluo-3 and indo-1 on an ACAS (Adherent Cell Analysis and Sorting) Laser Cytometer. Ethanol exerted a concentration-dependent inhibition of carbachol-stimulated PI metabolism. In addition, ethanol's inhibitory effect paralleled the temporal development of the muscarinic receptor signal transduction system, with the strongest inhibition (25-50%) occurring when maximal stimulation by carbachol occurs (days 5-7). Ethanol also exerted a...Continue Reading

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Citations

May 8, 2000·Journal of Neuroscience Research·M C CatlinL G Costa
Jan 15, 1999·Molecular Neurobiology·S C Pandey
Jun 1, 1997·Alcoholism, Clinical and Experimental Research·J P ZhangG Y Sun
Jun 11, 1998·Alcoholism, Clinical and Experimental Research·C LarssonJ B Hoek
Apr 9, 1999·Alcoholism, Clinical and Experimental Research·K Yagle, L G Costa
Aug 14, 2009·Alcoholism, Clinical and Experimental Research·Kathryn L VanDemarkLucio G Costa
Sep 26, 2000·Cytometry·M C CatlinL G Costa

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