Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1981 Dec 15;200(3):509–514. doi: 10.1042/bj2000509

Heterologous desensitization of the cyclic AMP-independent glycogenolytic response in rat liver cells.

B Bréant, S Keppens, H De Wulf
PMCID: PMC1163571  PMID: 6123310

Abstract

Vasopressin and alpha-adrenergic agonists are known to be potent cyclic AMP-independent Ca2+-dependent activators of liver glycogen phosphorylase. When hepatocytes are pre-incubated with increasing concentrations of vasopressin or of the alpha-agonist phenylephrine, they become progressively unresponsive to a second addition of the respective agonist. The relative abilities of six vasopressin analogues and of five alpha-agonists to activate glycogen phosphorylase and to cause subsequent desensitization are highly correlated, indicating that the same vasopressin and alpha-adrenergic receptors are involved in both responses. About 5-times-higher peptide concentrations are needed to desensitize the cells than to activate their glycogen phosphorylase, whereas the concentrations of alpha-agonists required for the desensitization are only twice those needed for the activation of phosphorylase. The desensitization is not mediated by a perturbation in the agonist-receptor interaction. It is clearly heterologous, i.e. it is not agonist-specific, and must therefore involve a mechanism common to both series of agonists. The evidence for a role of Ca2+ movements or phosphatidylinositol turnover is briefly discussed.

Full text

PDF
509

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aggerbeck M., Guellaen G., Hanoune J. The alpha-adrenergic mediated effect in rat liver. Correlation between [3H]-dihydroergocryptine binding to plasma membranes and glycogen phosphorylase activation in isolated hepatocytes. Biochem Pharmacol. 1980 Jun 15;29(12):1653–1662. doi: 10.1016/0006-2952(80)90120-3. [DOI] [PubMed] [Google Scholar]
  2. Althaus-Salzmann M., Carafoli E., Jakob A. Ca2+, K+ redistributions and alpha-adrenergic activation of glycogenolysis in perfused rat livers. Eur J Biochem. 1980 May;106(1):241–248. doi: 10.1111/j.1432-1033.1980.tb06015.x. [DOI] [PubMed] [Google Scholar]
  3. Babcock D. F., Chen J. L., Yip B. P., Lardy H. A. Evidence for mitochondrial localization of the hormone-responsive pool of Ca2+ in isolated hepatocytes. J Biol Chem. 1979 Sep 10;254(17):8117–8120. [PubMed] [Google Scholar]
  4. Barritt G. J., Parker J. C., Wadsworth J. C. A kinetic analysis of the effects of adrenaline on calcium distribution in isolated rat liver parenchymal cells. J Physiol. 1981 Mar;312:29–55. doi: 10.1113/jphysiol.1981.sp013614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blackmore P. F., Brumley F. T., Marks J. L., Exton J. H. Studies on alpha-adrenergic activation of hepatic glucose output. Relationship between alpha-adrenergic stimulation of calcium efflux and activation of phosphorylase in isolated rat liver parenchymal cells. J Biol Chem. 1978 Jul 25;253(14):4851–4858. [PubMed] [Google Scholar]
  6. Blackmore P. F., Dehaye J. P., Exton J. H. Studies on alpha-adrenergic activation of hepatic glucose output. The role of mitochondrial calcium release in alpha-adrenergic activation of phosphorylase in perfused rat liver. J Biol Chem. 1979 Aug 10;254(15):6945–6950. [PubMed] [Google Scholar]
  7. Cantau B., Keppens S., De Wulf H., Jard S. (3H)-vasopressin binding to isolated rat hepatocytes and liver membranes: regulation by GTP and relation to glycogen phosphorylase activation. J Recept Res. 1980;1(2):137–168. doi: 10.3109/10799898009044096. [DOI] [PubMed] [Google Scholar]
  8. Chen J. L., Babcock D. F., Lardy H. A. Norepinephrine, vasopressin, glucagon, and A23187 induce efflux of calcium from an exchangeable pool in isolated rat hepatocytes. Proc Natl Acad Sci U S A. 1978 May;75(5):2234–2238. doi: 10.1073/pnas.75.5.2234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. El-Refai M. F., Blackmore P. F., Exton J. H. Evidence for two alpha-adrenergic binding sites in liver plasma membranes. Studies with [3H]epinephrine and [3H]dihydroergocryptine. J Biol Chem. 1979 Jun 10;254(11):4375–4386. [PubMed] [Google Scholar]
  10. Fain J. N., García-Sáinz J. A. Role of phosphatidylinositol turnover in alpha 1 and of adenylate cyclase inhibition in alpha 2 effects of catecholamines. Life Sci. 1980 Apr 14;26(15):1183–1194. doi: 10.1016/0024-3205(80)90062-4. [DOI] [PubMed] [Google Scholar]
  11. Keppens S., de Wulf H. The nature of the hepatic receptors involved in vasopressin-induced glycogenolysis. Biochim Biophys Acta. 1979 Nov 15;588(1):63–69. doi: 10.1016/0304-4165(79)90371-4. [DOI] [PubMed] [Google Scholar]
  12. Kirk C. J., Michell R. H., Hems D. A. Phosphatidylinositol metabolism in rat hepatocytes stimulated by vasopressin. Biochem J. 1981 Jan 15;194(1):155–165. doi: 10.1042/bj1940155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kirk C. J., Rodrigues L. M., Hems D. A. The influence of vasopressin and related peptides on glycogen phosphorylase activity and phosphatidylinositol metabolism in hepatocytes. Biochem J. 1979 Feb 15;178(2):493–496. doi: 10.1042/bj1780493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lefkowitz R. J., Wessels M. R., Stadel J. M. Hormones, receptors, and cyclic AMP: their role in target cell refractoriness. Curr Top Cell Regul. 1980;17:205–230. doi: 10.1016/b978-0-12-152817-1.50011-0. [DOI] [PubMed] [Google Scholar]
  15. Michell R. H. Inositol phospholipids and cell surface receptor function. Biochim Biophys Acta. 1975 Mar 25;415(1):81–47. doi: 10.1016/0304-4157(75)90017-9. [DOI] [PubMed] [Google Scholar]
  16. Michell R. H., Kirk C. J., Billah M. M. Hormonal stimulation of phosphatidylinositol breakdown with particular reference to the hepatic effects of vasopressin. Biochem Soc Trans. 1979 Oct;7(5):861–865. doi: 10.1042/bst0070861. [DOI] [PubMed] [Google Scholar]
  17. Murphy E., Coll K., Rich T. L., Williamson J. R. Hormonal effects on calcium homeostasis in isolated hepatocytes. J Biol Chem. 1980 Jul 25;255(14):6600–6608. [PubMed] [Google Scholar]
  18. Poggioli J., Berthon B., Claret M. Calcium movements in in situ mitochondria following activation of alpha-adrenergic receptors in rat liver cells. FEBS Lett. 1980 Jun 30;115(2):243–246. doi: 10.1016/0014-5793(80)81178-1. [DOI] [PubMed] [Google Scholar]
  19. Schmelck P. H., Hanoune J. The hepatic adrenergic receptors. Mol Cell Biochem. 1980 Dec 10;33(1-2):35–48. doi: 10.1007/BF00224570. [DOI] [PubMed] [Google Scholar]
  20. Tolbert M. E., White A. C., Aspry K., Cutts J., Fain J. N. Stimulation by vasopressin and alpha-catecholamines of phosphatidylinositol formation in isolated rat liver parenchymal cells. J Biol Chem. 1980 Mar 10;255(5):1938–1944. [PubMed] [Google Scholar]
  21. Vandenheede J. R., Keppens S., De Wulf H. The activation of liver phosphorylase b kinase by glucagon. FEBS Lett. 1976 Jan 15;61(2):213–217. doi: 10.1016/0014-5793(76)81040-x. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES