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. 1984 Jun 1;220(2):441–445. doi: 10.1042/bj2200441

Glycogenolytic effects of the calcium ionophore A23187, but not of vasopressin or angiotensin, in foetal-rat hepatocytes.

M Freemark, S Handwerger
PMCID: PMC1153645  PMID: 6430282

Abstract

Vasopressin, angiotensin and phenylephrine stimulate glycogenolysis in postnatal rat liver by a Ca2+-mediated mechanism not involving cyclic AMP. To determine whether these hormones promote glycogenolysis in foetal liver, we have examined their effects, and those of the Ca2+ ionophore A23187, on glycogen metabolism in cultured foetal-rat hepatocytes. Vasopressin and angiotensin (0.1 nM-0.1 microM) had no effects on either glycogen synthesis (as assessed by [14C]glucose incorporation into glycogen) or phosphorylase a activity. However, A23187 at 1 and 10 microM inhibited glycogen synthesis by 31.3 and 89.1% respectively (both P less than 0.001) and stimulated phosphorylase a activity by 66.9 and 184.1% respectively (both P less than 0.01). Incubation of cells in Ca2+-deficient medium attenuated the effects of 10 microM-A23187 on glycogen synthesis and abolished the effects of 1 microM-A23187. As in postnatal liver, glucagon (1 and 20 nM) and isoprenaline (1 and 10 microM), which activate adenylate cyclase, inhibited glycogen synthesis and stimulated phosphorylase a activity in foetal hepatocytes. The minimal effective concentration of phenylephrine was 10 times that of isoprenaline. These results indicate striking differences in the ontogeny of cyclic AMP-mediated and Ca2+-mediated processes which regulate hepatic glycogenolysis. Since increases in cytosolic Ca2+ induce glycogenolysis in foetal-rat liver, the weak or absent responses to vasopressin, angiotensin and the alpha-adrenergic agonists may result from defects in hormone-receptor binding or in post-receptor events leading to the mobilization of intracellular Ca2+ stores.

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Selected References

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  1. Aggerbeck M., Guellaen G., Hanoune J. Adrenergic receptor of the alpha 1-subtype mediates the activation of the glycogen phosphorylase in normal rat liver. Biochem Pharmacol. 1980 Feb 15;29(4):643–645. doi: 10.1016/0006-2952(80)90389-5. [DOI] [PubMed] [Google Scholar]
  2. Blackmore P. F., Hughes B. P., Shuman E. A., Exton J. H. alpha-Adrenergic activation of phosphorylase in liver cells involves mobilization of intracellular calcium without influx of extracellular calcium. J Biol Chem. 1982 Jan 10;257(1):190–197. [PubMed] [Google Scholar]
  3. 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]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  5. Butlen D., Guillon G., Cantau B., Jard S. Comparison of the developmental patterns of vasopressin, glucagon and alpha-adrenergic receptors from rat-liver membranes. Mol Cell Endocrinol. 1980 Sep;19(3):275–289. doi: 10.1016/0303-7207(80)90057-x. [DOI] [PubMed] [Google Scholar]
  6. Bär H. P., Hahn P. Development of rat liver adenylcyclase. Can J Biochem. 1971 Jan;49(1):85–89. doi: 10.1139/o71-013. [DOI] [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. Chan T. M., Exton J. H. A rapid method for the determination of glycogen content and radioactivity in small quantities of tissue or isolated hepatocytes. Anal Biochem. 1976 Mar;71(1):96–105. doi: 10.1016/0003-2697(76)90014-2. [DOI] [PubMed] [Google Scholar]
  9. Christoffersen T., Morland J., Osnes J. B., Oye I. Development of cyclic AMP metabolism in rat liver. A correlative study of tissue levels of cyclic AMP, accumulation of cyclic AMP in slices, adenylate cyclase activity and cyclic nucleotide phosphodiesterase activity. Biochim Biophys Acta. 1973 Jul 28;313(2):338–349. doi: 10.1016/0304-4165(73)90033-0. [DOI] [PubMed] [Google Scholar]
  10. Creba J. A., Downes C. P., Hawkins P. T., Brewster G., Michell R. H., Kirk C. J. Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones. Biochem J. 1983 Jun 15;212(3):733–747. doi: 10.1042/bj2120733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Exton J. H. Mechanisms involved in alpha-adrenergic phenomena: role of calcium ions in actions of catecholamines in liver and other tissues. Am J Physiol. 1980 Jan;238(1):E3–12. doi: 10.1152/ajpendo.1980.238.1.E3. [DOI] [PubMed] [Google Scholar]
  12. Exton J. H. Mechanisms involved in effects of catecholamines on liver carbohydrate metabolism. Biochem Pharmacol. 1979 Aug 1;28(15):2237–2240. doi: 10.1016/0006-2952(79)90684-1. [DOI] [PubMed] [Google Scholar]
  13. Freemark M., Handwerger S. Ovine placental lactogen stimulates glycogen synthesis in fetal rat hepatocytes. Am J Physiol. 1984 Jan;246(1 Pt 1):E21–E24. doi: 10.1152/ajpendo.1984.246.1.E21. [DOI] [PubMed] [Google Scholar]
  14. Golden S., Wals P. A., Katz J. An improved procedure for the assay of glycogen synthase and phosphorylase in rat liver homogenates. Anal Biochem. 1977 Feb;77(2):436–445. doi: 10.1016/0003-2697(77)90257-3. [DOI] [PubMed] [Google Scholar]
  15. Hems D. A., Whitton P. D. Control of hepatic glycogenolysis. Physiol Rev. 1980 Jan;60(1):1–50. doi: 10.1152/physrev.1980.60.1.1. [DOI] [PubMed] [Google Scholar]
  16. Ichihara A., Nakamura T., Tanaka K. Use of hepatocytes in primary culture for biochemical studies on liver functions. Mol Cell Biochem. 1982 Apr 2;43(3):145–160. doi: 10.1007/BF00223006. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Litosch I., Lin S. H., Fain J. N. Rapid changes in hepatocyte phosphoinositides induced by vasopressin. J Biol Chem. 1983 Nov 25;258(22):13727–13732. [PubMed] [Google Scholar]
  19. McMillian M. K., Schanberg S. M., Kuhn C. M. Ontogeny of rat hepatic adrenoceptors. J Pharmacol Exp Ther. 1983 Oct;227(1):181–186. [PubMed] [Google Scholar]
  20. Moncany M. L., Plas C. Interaction of glucagon and epinephrine in the regulation of adenosine 3',5'-monophosphate-dependent glycogenolysis in the cultured fetal hepatocyte. Endocrinology. 1980 Dec;107(6):1667–1675. doi: 10.1210/endo-107-6-1667. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Strickland W. G., Blackmore P. F., Exton J. H. The role of calcium in alpha-adrenergic inactivation of glycogen synthase in rat hepatocytes and its inhibition by insulin. Diabetes. 1980 Aug;29(8):617–622. doi: 10.2337/diab.29.8.617. [DOI] [PubMed] [Google Scholar]
  23. Wood C. L., Babcock C. J., Blum J. J. Effects of vasopressin on carbohydrate metabolism in hepatocytes from dehydrated rats. Proc Soc Exp Biol Med. 1981 May;167(1):129–136. doi: 10.3181/00379727-167-41137. [DOI] [PubMed] [Google Scholar]

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