Differential effects of ethanol on signal transduction.
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.
Levine
G H
GH
MCP Hahnemann School of Medicine, Allegheny University of Health Sciences, Philadelphia, Pennsylvania 19129, USA.
Maglio
J J
JJ
Horwitz
J
J
D000437:Alcoholism / Q000201:enzymology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D016716:PC12 Cells; D010739:Phospholipase D / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000431:Ethanol; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D010739:Phospholipase D; D001920:Bradykinin