Effects of chronic ethanol treatment on the angiotensin II-mediated p42/p44 mitogen-activated protein kinase and phosphorylase a activation in rat hepatocytes.
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.
Weng
Yu I
YI
Department of Pharmacology, School of Medicine, University of Missouri-Columbia, One Hospital Drive, Columbia, MO 65212, USA.
Shukla
Shivendra D
SD
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D015151:Immunoblotting; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010762:Phosphorylase a / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D000804:Angiotensin II; D000431:Ethanol; D010762:Phosphorylase a; D019950:Mitogen-Activated Protein Kinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium