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G Proteins Coupled to Phospholipase C: Molecular Targets of Long-Term Ethanol Exposure
Authors:Per Simonsson  F David Rodriguez  Niklas Loman  Christer Alling
Institution:Department of Psychiatry and Neurochemistry, Lund University, Sweden.
Abstract:Long-term ethanol exposure is known to inhibit bradykinin-stimulated phosphoinositide hydrolysis in cultures of neuroblastoma x glioma 108-15 cells. In the present study, 3H]bradykinin binding, GTP-binding protein function, and phospholipase C activity were assayed in cells grown for 4 days in 100 mM ethanol with the aim of elucidating the molecular target of ethanol on signal transduction coupled to inositol trisphosphate and diacylglycerol formation. Ethanol exposure reduced guanosine 5'-O-(3-thiotriphosphate) GTP(S)]- and, to a lesser extent, NaF/AlCl3-stimulated phosphoinositide hydrolysis, whereas it had no effect on the enzymatic activity of a phosphatidylinositol 4,5-bisphosphate-specific phospholipase C. 3H]Bradykinin binding in the absence of GTP(S) was not influenced by ethanol exposure. However, the reduction in 3H]bradykinin binding seen in control cells after addition of GTP analogue was inhibited in cells grown in ethanol-containing medium. The results indicate that long-term ethanol exposure exerts its effects on receptor-stimulated phosphoinositide hydrolysis primarily at the level of the GTP-binding protein.
Keywords:Ethanol  Bradykinin  Phosphatidylinositol 4  5-bisphosphate  Phospholipase C  GTP-binding protein  NG 108–15 cell line
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