Reexamination of the Second Messenger Hypothesis of Glucagon and Catecholamine Action in Liver
Glucagon causes a rapid activation of cAMP-dependent protein kinase in rat liver parenchymal cells which correlates well with the accumulation of cAMP. Full activation of phosphorylase or inactivation of glycogen synthase is achieved with half-maximal activation of protein kinase. Epinephrine stimulates glycogen breakdown and gluconeogenesis in these cells mainly by mechanisms involving α-adrenergic receptors and not β-receptors. Activation of α-receptors results in rapid activation of phosphorylase and inactivation of glycogen synthase without accumulation of cAMP or activation of cAMP-dependent protein kinase. Activation of β-receptors causes a transient rise in cAMP and a short-lived activation of protein kinase with correspondingly little stimulation of glycogenolysis and gluconeogenesis.
KeywordsLactate Adenosine Epinephrine Catecholamine Propranolol
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- 1.Assimacopoulos-Jeannet, F. D., Blackmore, P. F. and Exton, J. H. (1977): Studies on the α-adrenergic activation of hepatic glucose output. I II. Studies on the role of calcium in the a-adrenergic activation of phosphorylase. J. Biol. Chem. Submitted for publication.Google Scholar
- 3.Birnbaum, M. J. and Fain, J. N. (1977): Activation of protein kinase and glycogen phosphorylase in isolated rat liver cells by glucagon and catecholamines. J. Biol. Chem. (in press).Google Scholar
- 4.Cherrington, A. D., Assimacopoulos, F. D., Harper, S. C., Corbin, J. D., Park, C. R. and Exton, J. H. (1976): Studies on the α-adrenergic activation of hepatic glucose output. II. Investigation of the roles of adenosine 3’;5’-monophosphate and adenosine 3’:5’-monophosphate-dependent protein kinase in the actions of phenylephrine in isolated hepatocytes. J. Biol. Chem. 251, 5209–5218.PubMedGoogle Scholar
- 5.DeWulf, H. and Keppens, S. (1975): Is calcium the second messenger in liver for cyclic AMP-independent glycogenolytic hormones? Arch. Intern. Physiol. Biochim. 84, 159–160.Google Scholar
- 6.Exton, J. H. and Harper, S. C. (1975): Role of cyclic AMP in the actions of catecholamines on hepatic carbohydrate metabolism. Adv. Cyclic Nucleotide Res. 5, 519–532.Google Scholar
- 10.Hutson, N. J., Brumley, F. T., Assimacopoulos, F. D., Harper, S. C. and Exton, J. H. (1976): Studies on the a-adrenergic activation of hepatic glucose output. I. Studies on the a-adrenergic activation of phosphorylase and gluconeogenesis and inactivation of glycogen synthase in isolated rat liver parenchymal cells. J. Biol. Chem. 251, 5200–5208.PubMedGoogle Scholar
- 11.Jakob, A. and Diem, S. (1976): Metabolic responses of perfused rat livers to alpha- and beta-adrenergic agonists, glucagon and cyclic AMP. Biochim. Biophys. Acta 404, 57–66.Google Scholar
- 14.Kneer, N. M., Bosch, A. L., Clark, M. G. and Lardy, H. A. (1974): Glucose inhibition of epinephrine stimulation of hepatic gluconeogenesis by blockade of the a-receptor function. Proc. Natl. Acad. Sci. 71, 4523–4527.Google Scholar
- 15.Moran, N. C. (1975): Adrenergic receptors. In: Handbook of Physiology. Section 7: Endocrinology, Vol. 6. Adrenal Gland. H. Blaschko, G. Sayer and A. D. Smith, Eds. American Physiological Society, Washington, D. C., pp. 447–472.Google Scholar
- 16.Newton, N. E. and Hornbrook, K. R. (1972): Effects of adrenergic agents on carbohydrate metabolism of rat liver: activities of adenyl cyclase and glycogen phosphorylase. J. Pharm. Exp. Ther. 181, 479–488.Google Scholar
- 22.Soderling, T. R. and Park, C. R. (1974): Recent advances in glycogen metabolism. In: Advances in Cyclic Nucleotide Research, Vol. 4. P. Greengard and G. A. Robison, Eds. Raven Press, New York, pp. 283–333.Google Scholar
- 24.Thomas, J. A., Schlender, K. K. and Larner, J. (1968): A rapid filter paper assay for UDP glucose-glycogen glucosyltransferase, including an improved biosynthesis of UDP-14c-glucose. Anal. Biochem. 486–499.Google Scholar