1994 Fiscal Year Final Research Report Summary
Effect of chronic ethanol feeding on intracellular signal transduction process in hepatocytes
| Project/Area Number |
04670441
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Nagoya City University |
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Principal Investigator |
HIGASHI Katsuyoshi Nagoya City University Medical School First Department of Internal Medicine Assistant Professor, 医学部, 助手 (30238266)
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| Project Period (FY) |
1992 – 1994
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| Keywords | chronic ethanol-fed rats / hepatocytes / signal transduction / phospholipase C / ethanol / vasopressin / protein kinase C / protein kinase A |
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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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