Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
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Research Abstract |
Effect of chronic ethanol feeding on phospholipase C (PLC) -mediated signal transduction processes in isolated rat hepatocytes. Ethanol-induced phospholipase C activation(intracellular Ca^<2+> ([Ca^<2+>]c) mobilization and inositol-trisphosphate (IP3) accumulation)was unaffected in the cells from control and chronically ethanol-fed rats. However, the responses to ethanol was more sustained in the cells from ethanol-fed rats. In intact cells, IP3 inctrased to the same levels in both preparations, but [Ca^<2+>] c mobilization was more enhanced in the cells from ethanolfed rats. In the permeabilized cells, IP3-induced Ca^<2+> release was more enhanced and sustained in the cells from ethanol-fed rats, indicating that the sensitivity of IP3 to the receptor and the activity of ATP-dependent Ca^<2+> pump decreased in the Ca^<2+> storage sites by chronic ethanol feeding. Vasopressin-induced PLC activation was inhibited by pretreating with phorbol ester, a protein kinase C activating agent, and was enhanced by cAMP-analog, a protein kinase A activating agent, in both preparations. The sensitivity to these agents was decreased in the cells from ethanol-fed rats. In addition the inhibitory effects of ethanol on the vasopressin-induced PLC activation decreased in the ethanol-fed preparations. These data demonstrated that chronic ethanol feeding causes a tolerance to ethanol and protein kinases in hormone-mediated PLC activation. It is suggested that chronic ethanol causes changes in PLC-mediated signal transduction processes and its cross talk, resulting to affect the expression of cell functions.
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