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Differential Effects of Ethanol on Signal Transduction
Author(s) -
Levine Gail H.,
Maglio Jeff J.,
Horwitz Joel
Publication year - 2000
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2000.tb04558.x
Subject(s) - bradykinin , phospholipase c , phospholipase d , bradykinin receptor , signal transduction , phospholipase , phosphatidylethanol , tyrosine kinase , chemistry , protein kinase c , phospholipase a2 , inositol , biochemistry , biology , microbiology and biotechnology , receptor , enzyme , phospholipid , phosphatidylcholine , membrane
Background: PC12 pheochromocytoma cells were used as a model to study the effect of long‐term ethanol exposure on signal transduction systems. In PC12 cells, the agonist bradykinin stimulates a phospholipase C specific for inositol‐containing phospholipids and a phospholipase D specific for phosphatidylcholine. Methods: PC12 cells were grown in monolayer and cultured in the presence and absence of 1% ethanol for 5 days. After this period, bradykinin‐stimulated phospholipase C and D were measured. The effect of long‐term ethanol on the bradykinin‐mediated activation of mitogen‐activated protein (MAP) kinase was also measured. Results: In cells exposed to 1% ethanol for 5 days, bradykinin‐stimulated phospholipase D was greatly attenuated, whereas bradykinin‐stimulated phospholipase C was not altered. The tyrosine kinase inhibitor, genistein, blocked the bradykinin‐mediated activation of phospholipase D but did not affect the stimulation of phospholipase C. However, long‐term ethanol treatment did not attenuate the ability of bradykinin to activate MAP kinase, which suggests that ethanol did not have a general effect on all tyrosine kinase pathways. Conclusions: Ethanol has a differential effect on signal transduction in PC12 cells. Activation of phospholipase D may be mediated by a kinase, whereas the activation of phospholipase C is probably mediated by the guanine nucleotide binding protein, Gq. Because of these differences in activation mechanism, the pathways may adapt differently to long‐term exposure to ethanol.