Differential effects of ethanol on signal transduction

Background: PC12 pheochromocytoma cells were used as a model to study the e ffect of long-term ethanol exposure on signal transduction systems. In PC12 cells, the agonist bradykinin stimulates a phospholipase C specific for in ositol-containing phospholipids and a phospholipase D specific for phosphat idylcholine. Methods: PC12 cells were grown in monolayer and cultured in the presence an d absence of 1% ethanol for 5 days. After this period, bradykinin-stimulate d phospholipase C and D were measured. The effect of long-term ethanol on t he bradykinin-mediated activation of mitogen-activated protein (MAP) kinase was also measured. Results: In cells exposed to 1% ethanol for 5 days, bradykinin-stimulated p hospholipase D was greatly attenuated, whereas bradykinin-stimulated phosph olipase C was not altered. The tyrosine kinase inhibitor, genistein, blocke d the bradykinin-mediated activation of phospholipase D but did not affect the stimulation of phospholipase C. However, long-term ethanol treatment di d not attenuate the ability of bradykinin to activate MAP kinase, which sug gests that ethanol did not have a general effect on all tyrosine kinase pat hways. Conclusions: Ethanol has a differential effect on signal transduction in PC 12 cells. Activation of phospholipase D may be mediated by a kinase, wherea s the activation of phospholipase C is probably mediated by the guanine nuc leotide binding protein, Gq. Because of these differences in activation mec hanism, the pathways may adapt differently to long-term exposure to ethanol .