© 1983 Oxford University Press
research-article |
The Perturbation of Hepatic Glutathione by 
2-Adrenergic Agonists
ADivision of Interdisciplinary Toxicology, University of Arkansas for Medical Sciences Little Rock, AR 72205 BPharmacology Section, College of Pharmacy, University of Cincinnati Medical Center Cinciannati, OH 45267
The Perturbation of Hepatic Glutathione by 
2 -Adrenergic Agonists. James, Robert C, Roberts, Stephen M. and Harbison, Raymond D. (1983). Fundam. Appl. Toxicol.. 3: 303–308. 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 2 receptors. Adrenergic antagonists with 2 receptor blocking properties, phenotolamine and yohimbine, prevented the epinephrine-induced lowering of GSH while agonists with 2 activity, clonidine and guanabenz, mimicked epinephrine's response. Antagonists with either 1or ß activity, i.e. prazosin, phenoxybenzamine and propranolol, did not prevent the epinephrine-induced lowering of hepatic GSH. Contrary to these findings antagonists with either or P 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 hepatocellular processes.