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. 1987 Sep 1;246(2):331–336. doi: 10.1042/bj2460331

Homologous beta-adrenergic desensitization in isolated rat hepatocytes.

J A García-Sáinz 1, B Michel 1
PMCID: PMC1148281  PMID: 2825633

Abstract

Hepatocytes from hypothyroid rats have a marked beta-adrenergic responsiveness. Preincubation of these hepatocytes with isoprenaline induced a time-dependent and concentration-dependent desensitization of the beta-adrenergic responsiveness without altering that to glucagon (homologous desensitization). The desensitization was evidenced both in the cyclic AMP accumulation and in the stimulation of ureagenesis induced by the beta-adrenergic agonists. Under the same conditions, preincubation with glucagon induced no desensitization. Propranolol was also unable to induce desensitization, but blocked that induced by isoprenaline. Pertussis-toxin treatment did not alter the homologous beta-adrenergic desensitization induced by isoprenaline.

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Selected References

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  1. Aggerbeck M., Ferry N., Zafrani E. S., Billon M. C., Barouki R., Hanoune J. Adrenergic regulation of glycogenolysis in rat liver after cholestasis. Modulation of the balance between alpha 1 and beta 2 receptors. J Clin Invest. 1983 Mar;71(3):476–486. doi: 10.1172/JCI110792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benovic J. L., Pike L. J., Cerione R. A., Staniszewski C., Yoshimasa T., Codina J., Caron M. G., Lefkowitz R. J. Phosphorylation of the mammalian beta-adrenergic receptor by cyclic AMP-dependent protein kinase. Regulation of the rate of receptor phosphorylation and dephosphorylation by agonist occupancy and effects on coupling of the receptor to the stimulatory guanine nucleotide regulatory protein. J Biol Chem. 1985 Jun 10;260(11):7094–7101. [PubMed] [Google Scholar]
  3. Benovic J. L., Strasser R. H., Caron M. G., Lefkowitz R. J. Beta-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. Proc Natl Acad Sci U S A. 1986 May;83(9):2797–2801. doi: 10.1073/pnas.83.9.2797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969 Dec;43(3):506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bitensky M. W., Russell V., Blanco M. Independent variation of glucagon and epinephrine responsive components of hepatic adenyl cyclase as a function of age, sex and steroid hormones. Endocrinology. 1970 Jan;86(1):154–159. doi: 10.1210/endo-86-1-154. [DOI] [PubMed] [Google Scholar]
  6. Blair J. B., James M. E., Foster J. L. Adrenergic control of glucose output and adenosine 3':5'-monophosphate levels in hepatocytes from juvenile and adult rats. J Biol Chem. 1979 Aug 25;254(16):7579–7584. [PubMed] [Google Scholar]
  7. Brown B. L., Albano J. D., Ekins R. P., Sgherzi A. M. A simple and sensitive saturation assay method for the measurement of adenosine 3':5'-cyclic monophosphate. Biochem J. 1971 Feb;121(3):561–562. doi: 10.1042/bj1210561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clark R. B., Goka T. J., Proll M. A., Friedman J. Homologous desensitization of beta-adrenergic receptors in lymphoma cells is not altered by the inactivation of Ni (Gi), the inhibitory guanine nucleotide regulatory protein. Biochem J. 1986 Apr 15;235(2):399–405. doi: 10.1042/bj2350399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Corvera S., Hernandez-Sotomayor S. M., Garcia-Sainz J. A. Modulation by thyroid status of cyclic AMP-dependent and Ca2+-dependent mechanisms of hormone action in rat liver cells. Possible involvement of two different transduction mechanisms in alpha 1-adrenergic action. Biochim Biophys Acta. 1984 Feb 17;803(1-2):95–105. doi: 10.1016/0167-4889(84)90060-0. [DOI] [PubMed] [Google Scholar]
  10. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gurr J. A., Ruh T. A. Desensitization of primary cultures of adult rat liver parenchymal cells to stimulation of adenosine 3',5'-monophosphate production by glucagon and epinephrine. Endocrinology. 1980 Nov;107(5):1309–1319. doi: 10.1210/endo-107-5-1309. [DOI] [PubMed] [Google Scholar]
  12. Harden T. K. Agonist-induced desensitization of the beta-adrenergic receptor-linked adenylate cyclase. Pharmacol Rev. 1983 Mar;35(1):5–32. [PubMed] [Google Scholar]
  13. Heyworth C. M., Hanski E., Houslay M. D. Islet-activating protein blocks glucagon desensitization in intact hepatocytes. Biochem J. 1984 Aug 15;222(1):189–194. doi: 10.1042/bj2220189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heyworth C. M., Houslay M. D. Challenge of hepatocytes by glucagon triggers a rapid modulation of adenylate cyclase activity in isolated membranes. Biochem J. 1983 Jul 15;214(1):93–98. doi: 10.1042/bj2140093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Huerta-Bahena J., Villalobos-Molina R., García-Saínz J. A. Roles of alpha 1- and beta-adrenergic receptors in adrenergic responsiveness of liver cells formed after partial hepatectomy. Biochim Biophys Acta. 1983 Sep 22;763(2):112–119. doi: 10.1016/0167-4889(83)90033-2. [DOI] [PubMed] [Google Scholar]
  16. Lam V., Bar H. P. Adrenaline-induced desensitization of liver adenylate cyclase. Biochem Pharmacol. 1976 Sep 15;25(18):2103–2104. doi: 10.1016/0006-2952(76)90439-1. [DOI] [PubMed] [Google Scholar]
  17. Lynch C. J., Prpic V., Blackmore P. F., Exton J. H. Effect of islet-activating pertussis toxin on the binding characteristics of Ca2+-mobilizing hormones and on agonist activation of phosphorylase in hepatocytes. Mol Pharmacol. 1986 Feb;29(2):196–203. [PubMed] [Google Scholar]
  18. Malbon C. C., Li S., Fain J. N. Hormonal activation of glycogen phosphorylase in hepatocytes from hypothyroid rats. J Biol Chem. 1978 Dec 25;253(24):8820–8825. [PubMed] [Google Scholar]
  19. Morgan N. G., Shuman E. A., Exton J. H., Blackmore P. F. Stimulation of hepatic glycogenolysis by alpha 1- and beta 2-adrenergic agonists. Evidence against short term agonist-induced desensitization of the responses. J Biol Chem. 1982 Dec 10;257(23):13907–13910. [PubMed] [Google Scholar]
  20. Nakamura T., Tomomura A., Noda C., Shimoji M., Ichihara A. Acquisition of a beta-adrenergic response by adult rat hepatocytes during primary culture. J Biol Chem. 1983 Aug 10;258(15):9283–9289. [PubMed] [Google Scholar]
  21. Noda C., Shinjyo F., Tomomura A., Kato S., Nakamura T., Ichihara A. Mechanism of heterologous desensitization of the adenylate cyclase system by glucagon in primary cultures of adult rat hepatocytes. J Biol Chem. 1984 Jun 25;259(12):7747–7754. [PubMed] [Google Scholar]
  22. Plas C., Nunez J. Glycogenolytic response to glucagon of cultured fetal hepatocytes. Refractoriness following prior exposure to glucagon. J Biol Chem. 1975 Jul 25;250(14):5304–5311. [PubMed] [Google Scholar]
  23. Pobiner B. F., Hewlett E. L., Garrison J. C. Role of Ni in coupling angiotensin receptors to inhibition of adenylate cyclase in hepatocytes. J Biol Chem. 1985 Dec 25;260(30):16200–16209. [PubMed] [Google Scholar]
  24. Reilly T. M., Blecher M. On the mechanism of isoproterenol-induced desensitization of adenylate cyclase in cultured differentiated hepatocytes. Biochim Biophys Acta. 1982 Apr 29;720(2):126–132. doi: 10.1016/0167-4889(82)90003-9. [DOI] [PubMed] [Google Scholar]
  25. Sekura R. D., Fish F., Manclark C. R., Meade B., Zhang Y. L. Pertussis toxin. Affinity purification of a new ADP-ribosyltransferase. J Biol Chem. 1983 Dec 10;258(23):14647–14651. [PubMed] [Google Scholar]
  26. Sherline P., Eisen H., Glinsmann W. Acute hormonal regulation of cyclic AMP content and glycogen phosphorylase activity in fetal liver in organ culture. Endocrinology. 1974 Apr;94(4):935–939. doi: 10.1210/endo-94-4-935. [DOI] [PubMed] [Google Scholar]
  27. Sibley D. R., Lefkowitz R. J. Molecular mechanisms of receptor desensitization using the beta-adrenergic receptor-coupled adenylate cyclase system as a model. Nature. 1985 Sep 12;317(6033):124–129. doi: 10.1038/317124a0. [DOI] [PubMed] [Google Scholar]
  28. Wilson P. D., Dixon B. S., Dillingham M. A., Garcia-Sainz J. A., Anderson R. J. Pertussis toxin prevents homologous desensitization of adenylate cyclase in cultured renal epithelial cells. J Biol Chem. 1986 Feb 5;261(4):1503–1506. [PubMed] [Google Scholar]

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