S R Aggarwal, C H Griffiths, K O Lindros, T N Palmer
{"title":"Effects of ethanol on glucagon-stimulated protein phosphorylation in isolated hepatocytes.","authors":"S R Aggarwal, C H Griffiths, K O Lindros, T N Palmer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Ethanol has profound acute effects on hepatic metabolism. While many of these effects are mediated via the redox imbalance that accompanies hepatic ethanol oxidation via the alcohol dehydrogenase (ADH) pathway, there is increasing evidence that ethanol also perturbs hepatic metabolism via its modulation of cyclic AMP-mediated signalling pathways. This paper examines the effects of ethanol on glucagon-stimulated protein phosphorylation using SDS-PAGE to analyse the 32P-labelling of cytosolic peptides in isolated rat hepatocytes pre-equilibrated with 32PO4(3-). We show that ethanol has biphasic effects on glucagon-stimulated protein phosphorylation. At a low concentration (50 mM), ethanol decreased the phosphorylation of certain peptides, whereas at higher concentrations (100-200 mM) it increased the 32P-labelling of all of the eleven glucagon-stimulated cytosolic peptides. The non-metabolizable alcohol 2-methylpyrazole-2-ol had no effects on glucagon-stimulated protein phosphorylation. The ADH inhibitor 4-methylpyrazole at 150 mM ethanol concentration abolished the potentiating effect of ethanol on the glucagon-stimulated phosphorylation of most peptides. In conclusion, the results indicate that ethanol alters glucagon-receptor-dependent protein phosphorylation in isolated hepatocytes via a complex mechanism that is partially dependent on ethanol oxidation via ADH.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24102761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}