Alcohol
Volume 29, Issue 2 , Pages 83-90, February 2003

Effects of chronic ethanol treatment on the angiotensin II–mediated p42/p44 mitogen-activated protein kinase and phosphorylase a activation in rat hepatocytes☆

  • Yu-I Weng

      Affiliations

    • Present address: Department of Ophthalmology, University of Cincinnati, Suite 350 HPB, 3223 Eden Avenue, Cincinnati, OH 45267, USA.
    • ,
  • Shivendra D Shukla

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +1-573-882-2740; fax: +1-573-884-4558.

Department of Pharmacology, School of Medicine, University of Missouri-Columbia, One Hospital Drive, Columbia, MO 65212, USA

Received 12 December 2001; received in revised form 20 November 2002; accepted 22 November 2002.

Abstract 

We have demonstrated previously that 24 h of ethanol treatment potentiates angiotensin II (ANG II)–stimulated p42/p44 mitogen-activated protein kinase (MAPK) activity in hepatocytes. This potentiation of p42/p44 MAPK by ethanol exhibited agonist selectivity. To compare the effects of acute (24 h) versus chronic (6 weeks) ethanol treatment, ANG II-induced intracellular signaling was examined in (1) rat hepatocytes treated with ethanol for 24 h and (2) hepatocytes obtained from rats fed ethanol for 6 weeks. In hepatocytes obtained from rats fed ethanol for 6 weeks, ANG II-stimulated phosphorylase a was reduced, and this activity was calcium dependent and p42/p44 MAPK independent. Surprisingly, ANG II-stimulated p42/p44 MAPK activation was not affected in hepatocytes obtained from rats fed ethanol chronically (6 weeks). However, chronic (6 weeks) ethanol treatment decreased ethanol potentiation of p42/p44 MAPK by about 56.3% ± 3.6% for p42 MAPK and 61.3% ± 11.7% for p44 MAPK. Furthermore, ethanol had no effect on the expression of angiotensinogen and c-myc mRNA in hepatocytes. A decrease in ANG II-activated phosphorylase a, but not in p42/p44 MAPK activation, after chronic (6 weeks) ethanol treatment leads to the conclusion that they may not be dependent on each other.

Keywords:  Angiotensin II, Ethanol, Hepatocytes, Mitogen-activated protein kinase, Phosphorylase a

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☆ Editor: T.R. Jerrells

PII: S0741-8329(02)00325-7

doi:10.1016/S0741-8329(02)00325-7

Alcohol
Volume 29, Issue 2 , Pages 83-90, February 2003

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