Differential Effect of Glutathione Depletion on Glycogenolysis in Isolated Rat Hepatocytes Mediated by a-Adrenoceptor Agonists and Glucagon
Glutathione (GSH) exerts a variety of cytoprotecive effects, but is readily depleted from cells under a variety of stressful stimuli. The impact of GSH depletion on receptor-mediated activity in rat hepatocytes has been studied with regard to glycogenolysis stimulated with a-adrenoceptor agonists or glucagon, which exert their actions through different signalling pathways. Depletion of GSH content (70%) by diethyl maleate had no effect on the redox status of the cells or on basal or glucagon-stimulated glycogenolysis, but significantly reduced the response to the a-adrenoceptor agonists adrenalin and phenylephrine. These results highlight the possible modulatory effects of GSH on receptor-mediated activity in hepatocytes.
Differential Effect of Glutathione Depletion on Glycogenolysis in Isolated Rat Hepatocytes Mediated by a-Adrenoceptor Agonists and Glucagon
Glutathione (GSH) exerts a variety of cytoprotecive effects, but is readily depleted from cells under a variety of stressful stimuli. The impact of GSH depletion on receptor-mediated activity in rat hepatocytes has been studied with regard to glycogenolysis stimulated with a-adrenoceptor agonists or glucagon, which exert their actions through different signalling pathways. Depletion of GSH content (70%) by diethyl maleate had no effect on the redox status of the cells or on basal or glucagon-stimulated glycogenolysis, but significantly reduced the response to the a-adrenoceptor agonists adrenalin and phenylephrine. These results highlight the possible modulatory effects of GSH on receptor-mediated activity in hepatocytes.
___
- Atmaca M, Hammond AH, Fry JR. Evaluation of a commercial kit for glutathione determination in cellular systems. ATLA 25: 667- 673, 1997.
- Dhanjal P, Fry JR. Determinants of MTT reduction in rat hepatocytes. Biomarkers 2: 111-116, 1997.
- Wagle SR, Ingebretsen WR. Stimulation of glycogenolysis by epinephrine and glucagon and its inhibition by insulin in isolated rat liver hepatocytes. Biochem Biophys Res Commun 52: 125- 129, 1973.
- Hutson NJ, Brumley FT, Assimacopoulos FD et al. Studies on the alpha-adrenergic activation of hepatic glucose output. I. Studies on the alpha-adrenergic activation of phosphorylase and gluconeogenesis and inactivation of glycogen synthase in isolated rat liver parenchymal cells. J Biol Chem 251: 5200-5208, 1976.
- Krack G, Goethals F, Deboyser D et al. Interference of chemicals with glycogen metabolism in isolated hepatocytes. Toxicology 18: 213-223, 1980.
- Reader TA, Briere R, Grondin L. Alpha-1 and alpha-2 adrenoceptor binding in cerebral cortex: role of disulfide and sulfhydryl groups. Neurochem Res 11: 9-27, 1986.
- Lipson KE, Kolhatkar AA, Dorato A et al. N-ethylmaleimide uncouples the glucagon receptor from the regulatory component of adenylyl cyclase. Biochemistry 25: 5678-5685, 1986.
- Wortsman J. Role of epinephrine in acute stress. Endocrinol Metab Clin North Am 31: 79-106, 2002.
- Taylor CG, Nagy LE, Bray TM. Nutritional and hormonal regulation of glutathione homeostasis. Curr Topic Cell Reg 34: 189-208, 1996.
- Fouin-Fortunet H, Delarue J, n’Djitoyap C et al. Nutritional status modifies glutathione levels in man. Eur J Gastroenterol Hepatol 2: 271-275, 1990.