Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1996 Jun 15;316(Pt 3):743–749. doi: 10.1042/bj3160743

A role of asialoglycoproteins for plasma-membrane-induced inhibition of the switching from alpha 1 to beta subtypes in adrenergic response during primary culture of rat hepatocytes.

Y Kajiyama 1, Y Sanai 1, M Ui 1
PMCID: PMC1217413  PMID: 8670147

Abstract

Adrenergic responses of rat hepatocytes were studied by measuring Ins(1,4,5)P3(for the response via alpha 1-subtype receptors) and cAMP (for beta-subtype response) generation during brief incubation of cells with respective agonists. Hepatocytes from young rats with an age of 1 week displayed a very high beta response without a significant alpha 1 response. The beta response decreased and the alpha 1 response increased progressively as the age increased; the response was almost exclusively via alpha 1 receptors in hepatocytes of adult rats 9 weeks or more old. The beta response developed, again at the expense of the alpha 1 response, in hepatocytes from adult rats during the primary culture at low cell densities [(1-2.5) x 10(4) cells/cm2]. Such "alpha 1 to beta subtype switching' of adrenergic responses in vitro was totally inhibited by adding plasma membranes prepared from adult rat liver into the low-cell-density culture, but not inhibited at all by membranes from young rat liver. The inhibitory effect of adult rat liver membranes was lost when the membranes had been exposed to endoglycosidase F or beta-galactosidase but was not affected by prior treatment with sialidase. On the contrary, young rat liver membranes became inhibitory to "alpha 1 to beta subtype switching' after prior treatment with sialidase. Thus glycoproteins with unsialylated galactosyl termini on the surface of adult rat hepatocytes are likely to function as a determinant of the relative development of alpha 1/beta subtypes of adrenergic responses; the beta response is predominant in hepatocytes in the juvenile, presumably as a result of sialylation of the galactosyl termini of the functional glycoproteins.

Full Text

The Full Text of this article is available as a PDF (497.1 KB).

Selected References

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

  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. 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]
  3. Conti Devirgiliis L., Massimi M., Bruscalupi G., Felici A., Dini L. Regulation of asialoglycoprotein receptor expression in rat hepatocytes cultured under proliferative conditions. Exp Cell Res. 1994 Jan;210(1):123–129. doi: 10.1006/excr.1994.1018. [DOI] [PubMed] [Google Scholar]
  4. Enrich C., Gahmberg C. G. Characterization of plasma-membrane glycoproteins from functional domains of the rat hepatocyte. Biochem J. 1985 Apr 15;227(2):565–572. doi: 10.1042/bj2270565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. García-Sáinz J. A., Nájera-Alvarado A. Hormonal responsiveness of liver cells during the liver regeneration process induced by carbon tetrachloride administration. Biochim Biophys Acta. 1986 Jan 23;885(1):102–109. doi: 10.1016/0167-4889(86)90044-3. [DOI] [PubMed] [Google Scholar]
  6. Goodhardt M., Ferry N., Aggerbeck M., Hanoune J. The hepatic alpha 1-adrenergic receptor. Biochem Pharmacol. 1984 Mar 15;33(6):863–868. doi: 10.1016/0006-2952(84)90439-8. [DOI] [PubMed] [Google Scholar]
  7. Guellaen G., Yates-Aggerbeck M., Vauquelin G., Strosberg D., Hanoune J. Characterization with [3H] dihydroergocryptine of the alpha-adrenergic receptor of the hepatic plasma membrane. Comparison with the beta-adrenergic receptor in normal and adrenalectomized rats. J Biol Chem. 1978 Feb 25;253(4):1114–1120. [PubMed] [Google Scholar]
  8. Howard D. J., Stockert R. J., Morell A. G. Asialoglycoprotein receptors in hepatic regeneration. J Biol Chem. 1982 Mar 25;257(6):2856–2858. [PubMed] [Google Scholar]
  9. Huerta-Bahena J., Villalobos-Molina R., Corvera S., García-Saínz J. A. Sensitivity of liver cells formed after partial hepatectomy to glucagon, vasopressin and angiotensin II. Biochim Biophys Acta. 1983 Sep 22;763(2):120–124. doi: 10.1016/0167-4889(83)90034-4. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Ishac E. J., Kunos G. An arachidonate metabolite is involved in the conversion from alpha 1- to beta-adrenergic glycogenolysis in isolated rat liver cells. Proc Natl Acad Sci U S A. 1986 Jan;83(1):53–57. doi: 10.1073/pnas.83.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Itoh H., Okajima F., Ui M. Conversion of adrenergic mechanism from an alpha- to a beta-type during primary culture of rat hepatocytes. Accompanying decreases in the function of the inhibitory guanine nucleotide regulatory component of adenylate cyclase identified as the substrate of islet-activating protein. J Biol Chem. 1984 Dec 25;259(24):15464–15473. [PubMed] [Google Scholar]
  13. Kajiyama Y., Ui M. Switching from alpha 1- to beta-subtypes in adrenergic response during primary culture of adult-rat hepatocytes as affected by the cell-to-cell interaction through plasma membranes. Biochem J. 1994 Oct 1;303(Pt 1):313–321. doi: 10.1042/bj3030313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Katz M. S., Boland S. R., Schmidt S. J. Developmental changes of beta-adrenergic receptor-linked adenylate cyclase of rat liver. Am J Physiol. 1985 Jun;248(6 Pt 1):E712–E718. doi: 10.1152/ajpendo.1985.248.6.E712. [DOI] [PubMed] [Google Scholar]
  15. Kunos G., Hirata F., Ishac E. J., Tchakarov L. Time-dependent conversion of alpha 1- to beta-adrenoceptor-mediated glycogenolysis in isolated rat liver cells: role of membrane phospholipase A2. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6178–6182. doi: 10.1073/pnas.81.19.6178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Malbon C. C. Liver cell adenylate cyclase and beta-adrenergic receptors. Increased beta-adrenergic receptor number and responsiveness in the hypothyroid rat. J Biol Chem. 1980 Sep 25;255(18):8692–8699. [PubMed] [Google Scholar]
  17. Morgan N. G., Blackmore P. F., Exton J. H. Age-related changes in the control of hepatic cyclic AMP levels by alpha 1- and beta 2-adrenergic receptors in male rats. J Biol Chem. 1983 Apr 25;258(8):5103–5109. [PubMed] [Google Scholar]
  18. Nakamura T., Tomomura A., Kato S., Noda C., Ichihara A. Reciprocal expressions of alpha 1- and beta-adrenergic receptors, but constant expression of glucagon receptor by rat hepatocytes during development and primary culture. J Biochem. 1984 Jul;96(1):127–136. doi: 10.1093/oxfordjournals.jbchem.a134804. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Noguchi A., Jett P. A., Gold A. H. cAMP-independent stimulation of glycogen phosphorylase in newborn rat hepatocytes. Am J Physiol. 1985 May;248(5 Pt 1):E560–E566. doi: 10.1152/ajpendo.1985.248.5.E560. [DOI] [PubMed] [Google Scholar]
  21. Oda-Tamai S., Kato S., Akamatsu N. Postnatal changes in sialylation of glycoproteins in rat liver. Biochem J. 1991 Nov 15;280(Pt 1):179–185. doi: 10.1042/bj2800179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Okajima F., Ui M. Conversion of adrenergic regulation of glycogen phosphorylase and synthase from an alpha to a beta type during primary culture of rat hepatocytes. Arch Biochem Biophys. 1982 Feb;213(2):658–668. doi: 10.1016/0003-9861(82)90596-3. [DOI] [PubMed] [Google Scholar]
  23. Okajima F., Ui M. Predominance of beta-adrenergic over alpha-adrenergic receptor functions involved in phosphorylase activation in liver cells of cholestatic rats. Arch Biochem Biophys. 1984 May 1;230(2):640–651. doi: 10.1016/0003-9861(84)90445-4. [DOI] [PubMed] [Google Scholar]
  24. Schleifer L. S., Black I. B., Reid L. M. Regulation of beta-adrenergic receptor expression in rat liver. J Cell Physiol. 1989 Jul;140(1):52–58. doi: 10.1002/jcp.1041400107. [DOI] [PubMed] [Google Scholar]
  25. Schwarz K. R., Lanier S. M., Carter E. A., Homcy C. J., Graham R. M. Rapid reciprocal changes in adrenergic receptors in intact isolated hepatocytes during primary cell culture. Mol Pharmacol. 1985 Feb;27(2):200–209. [PubMed] [Google Scholar]
  26. Spiess M. The asialoglycoprotein receptor: a model for endocytic transport receptors. Biochemistry. 1990 Oct 30;29(43):10009–10018. doi: 10.1021/bi00495a001. [DOI] [PubMed] [Google Scholar]
  27. Stein G. H., Atkins L. Membrane-associated inhibitor of DNA synthesis in senescent human diploid fibroblasts: characterization and comparison to quiescent cell inhibitor. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9030–9034. doi: 10.1073/pnas.83.23.9030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stockert R. J., Becker F. F. Diminished hepatic binding protein for desialylated glycoproteins during chemical hepatocarcinogenesis. Cancer Res. 1980 Oct;40(10):3632–3634. [PubMed] [Google Scholar]
  29. Tsujimoto A., Tsujimoto G., Azhar S., Hoffman B. B. Altered responsiveness to alpha- and beta-adrenoceptor stimulation in hepatocytes cultured in defined medium. Biochem Pharmacol. 1986 Apr 15;35(8):1400–1404. doi: 10.1016/0006-2952(86)90290-x. [DOI] [PubMed] [Google Scholar]
  30. Van der Smissen P., Vael T., Courtoy P. J., Baudhuin P. Ligand-induced clustering of asialoglycoprotein receptors on rat hepatocytes at 4 degrees C. Eur J Cell Biol. 1993 Feb;60(1):122–130. [PubMed] [Google Scholar]
  31. Weigel P. H. Galactosyl and N-acetylgalactosaminyl homeostasis: a function for mammalian asialoglycoprotein receptors. Bioessays. 1994 Jul;16(7):519–524. doi: 10.1002/bies.950160713. [DOI] [PubMed] [Google Scholar]
  32. Weigel P. H., Oka J. A. Coated pits and asialoglycoprotein receptors redistribute to the substratum during hepatocyte adhesion to galactoside surfaces. Biochem Biophys Res Commun. 1991 Nov 14;180(3):1304–1311. doi: 10.1016/s0006-291x(05)81337-3. [DOI] [PubMed] [Google Scholar]
  33. Weiss P., Ashwell G. Ligand-induced modulation of the hepatic receptor for asialoglycoproteins. Evidence for the role of cell surface hyposialylation. J Biol Chem. 1989 Jul 15;264(20):11572–11574. [PubMed] [Google Scholar]

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

RESOURCES