Author(s): Levine GH, Maglio JJ, Horwitz J
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Abstract 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.
This article was published in Alcohol Clin Exp Res
and referenced in Autism-Open Access