The perturbation of hepatic glutathione by alpha 2-adrenergic agonists.
Single injections of epinephrine significantly lowered the hepatocellular levels of reduced glutathione (GSH) while producing small but significant elevations in serum glutamic-pyruvic transaminase (SGPT) activity. Hormones, i.e. glucagon and the corticosteroids, were also found to depress significantly hepatic glutathione. Based upon the agonist-antagonist studies performed, the hepatic GSH lowering effects of epinephrine appear to be mediated solely by alpha 2 receptors. Adrenergic antagonists with alpha 2 receptor blocking properties, phenotolamine and yohimbine, prevented the epinephrine-induced lowering of GSH while agonists with alpha 2 activity, clonidine and guanabenz, mimicked epinephrine's response. Antagonists with either alpha 1 or beta activity, i.e. prazosin, phenoxybenzamine and propranolol, did not prevent the epinephrine-induced lowering of hepatic GSH. Contrary to these findings antagonists with either alpha or beta receptor blocking activity significantly reduced the epinephrine-induced elevations in SGPT activity. Thus, there was no apparent relationship between the elevation of SGPT activity and the reduction in hepatic glutathione levels. It is concluded that the therapeutic administration of these compounds, or physiologic responses to stress or pain, may exacerbate the hepatotoxicity of compounds detoxified by GSH or alter important glutathione-mediated hepatocellullar processes.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013256:Steroids / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D013256:Steroids; D000431:Ethanol; D000410:Alanine Transaminase; D005978:Glutathione; D004837:Epinephrine