Regulatory Effects of a Thromboxane A2Analogue on Hepatic Glycogenolysis and Vasoconstriction

  • Rory A. Fisher
  • Mark E. Steinhelper
  • Merle S. Olson
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Many studies have indicated that the regulatory effects of hormones on glycogenolysis in the rat liver occur by at least two distinct mechanisms. While glucagon andß-adrenergic agonists stimulate hepatic glycogenolysis via cAMP-dependent protein kinase activation,α-adrenergic hormones as well as vasopressin and angiotension II mediate their effects by mechanisms independent of cAMP (Hems and Whitton, 1980; Extonet al., 1981). Con vincing experimental evidence suggests that alterations in cellular calcium fluxes leading to increases in the cytosolic calcium concentration and subsequent activation of phosphorylase kinase are involved in the glycogenolytic actions of the cAMP-independent hormones (Blackmoreet al., 1978; Murphyet al., 1980). Studies in several laboratories have indicated a possible second-messenger role of inositol-1,4,5-trisphosphate, a breakdown product of phosphatidylinositol-4,5-bisophosphate, in the calcium-mobilizing properties of these hormones (Berridge, 1984; Williamsonet al., 1985). The glycogenolytic actions of both glucagon and calcium-mobilizing hormones are observed in isolated hepatocytes, which constitute approximately 90% of the liver volume and are the primary site of glycogen storage in the liver.


Glycogen Phosphorylase Perfuse Liver Arachidonic Acid Metabolite Glucose Release Hepatic Glucose Output 
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  1. Berridge, M. J., 1984, Inositol trisphosphate and diacylglycerol as second messengers, Biochem. J. 220:345–360.PubMedGoogle Scholar
  2. Blackmore, P. F., Brumley, F. T., Marks, J. L., and Exton, J. H., 1978, Studies on a-adrenergic activation of hepatic glucose output: Relationship between α-adrenergic stimulation of calcium efflux and activation of phosphorylase in isolated rat liver parenchymal cells, J. Biol. Chem. 253: 4851–4858.PubMedGoogle Scholar
  3. Blackmore, P. F., Dehaye, J.-P., and Exton, J. H., 1979, Studies on a-adrenergic activation of hepatic glucose output: The role of mitochondrial calcium release in α-adrenergic activation of phospho rylase in perfused rat liver, J. Biol. Chem. 254:6945–6950.PubMedGoogle Scholar
  4. Bowers, G. J., MacVittie, T. J., Hirsch, E. F., Conklin, J. C., Nelson, R. D., Roethel, R. J., and Fink, M. P., 1985, Prostanoid production by lipopolysaccharide-stimulated Kupffer cells, J. Surg. Res. 38:501–508.PubMedCrossRefGoogle Scholar
  5. Buxton, D. B., Fisher, R. A., Hanahan, D. J., and Olson, M. S., 1986, Platelet-activating factormediated vasoconstriction and glycogenolysis in the perfused rat liver, J. Biol. Chem. 261:644–649.PubMedGoogle Scholar
  6. Buxton, D. B., Fisher, R. A., Briseno, D. L., Hanahan, D. J., and Olson, M. S., 1987, Glycogenolytic and haemodynamic responses to heat-aggregated immunoglobulin G and prostaglandin E2 in the perfused rat liver, Biochem. J. 243:493–498.PubMedGoogle Scholar
  7. Buxton, D. B., Hanahan, D. J., and Olson, M. S., 1984, Stimulation of glycogenolysis and plateletactivating factor production by heat-aggregated immunoglobulin G in the perfused rat liver, J. Biol. Chem. 259:13758–13761.PubMedGoogle Scholar
  8. Exton, J. H., Blackmore, P. F., El-Refai, M. F., Dehaye, J.-P. Strickland, W. G., Cherrington, A. D., Chan, T. M., Assimacopoulos-Jeannet, F. D., andChrisman, T.D., 1981, Mechanisms of hormonal regulation of liver metabolism, Adv. Cyclic Nucleotide Res. 14:491–505.PubMedGoogle Scholar
  9. Fisher, R. A., Kumar, R., Hanahan, D. J., and Olson, M. S., 1986a, Effects of ß-adrenergic stimulation on 1-0-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine-mediated vasoconstriction and glycogenolysis in the perfused rat liver, J. Biol. Chem. 261:8817–8823.PubMedGoogle Scholar
  10. Fisher, R. A., Kumar, R., Hanahan, D. J., and Olson, M. S., 1986b, Stimulation of glycogenolysis and platelet-activating factor synthesis by zymosan in the perfused rat liver, Fed. Proc. 45:1838.Google Scholar
  11. Fisher, R. A., Robertson, S. M., and Olson, M. S., 1987, Stimulation of glycogenolysis and vasoconstriction in the perfused rat liver by the thromboxane A2 analogue U-46619, J. Biol. Chem. 262:4631–4638.PubMedGoogle Scholar
  12. Fisher, R. A., Shukla, S. D., Debuysere, M. S., Hanahan, D. J., and Olson, M. S., 1984, The effect of acetylglyceryl ether phosphorylcholine on glycogenolysis and phosphatidylinositol 4,5-bisphosphate metabolism in rat hepatocytes, J. Biol. Chem. 261:8685–8688.Google Scholar
  13. Hems, D. A., and Brosnan, J. T., 1970, Effects of ischemia on content of metabolites in rat liver and kidney in vivo, Biochem. J. 120:105–111.PubMedGoogle Scholar
  14. Hems, D. A., and Whitton, P. D., 1980, Control of hepatic glycogenolysis, Physiol. Rev. 60:1–50.PubMedGoogle Scholar
  15. Mahmud, I., and Miura, Y,, 1981, Effects of stimulators and inhibitors on arachidonic acid metabolism in hepatoma, Cell. Molec. Biol. 27:197–202.Google Scholar
  16. McCuskey, R. S., 1966, A dynamic and static study of hepatic arterioles and sphincters, Am. J. Anat. 119:455–477.PubMedCrossRefGoogle Scholar
  17. Murphy, E., Coll, K., Rich, T. L., and Williamson, J. R., 1980, Hormonal effects on calcium homeostasis in isolated hepatocytes, J. Biol. Chem. 255:6600–6608.PubMedGoogle Scholar
  18. Powell, W. J., 1982, Rapid extraction of arachidonic acid metabolites from biological samples using octadecylsilyl silica, in: Methods in Enzymology Vol. 86 (W.E.M. Lands and W. L. Smith, eds.), Academic Press, New York, pp. 467–477.Google Scholar
  19. Spolarics, Z., Tanacs, B., Garzo, T., Mandl, J., Mucha, I., Antoni, F., Machovich, R., andHorvath, I., 1984, Prostaglandin and thromboxane synthesizing activity in isolated murine hepatocytes and non-parenchymal liver cells, Prostaglandins Leukotrienes Med. 16:379–388.CrossRefGoogle Scholar
  20. Theen, J., Gilboe, D. P., and Nutall, F. Q., 1982, Liver glycogen synthase and phosphorylase changes in vivo with hypoxia and anaesthetics, Am. J. Physiol. 243:EI82–EI87.Google Scholar
  21. Williamson, J. R., Cooper, R. H., Joseph, S. K., and Thomas, A. P., 1985, Inositol trisphosphate and diacylglycerol as intracellular second messengers in liver, Am. J. Physiol. 248:C203–C216.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Rory A. Fisher
    • 1
  • Mark E. Steinhelper
    • 1
  • Merle S. Olson
    • 1
  1. 1.Department of BiochemistryUniversity of Texas Health Science CenterSan AntonioUSA

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