Prostaglandyl-Inositol Cyclic-Phosphate, A New Second Messenger

  • H. Wasner
  • H. Lemoine
  • E. Junger
  • M. Leßmann
  • R. Kaufmann
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


The main interest of the late Earl Sutherland was to prove or disprove the hypothetical existence of an intracellular regulator which antagonizes the action of cyclic AMP (1). A starting observation was, that following a first stimulation of hepatocytes with glucagon, it was possible to increase cyclic AMP levels also a second time. However, in the case of stimulation with adrenaline, cyclic AMP levels rise only a little bit on a first but not on a second stimulation (Fig. 1). The assumption was that in the latter case the adenylate cyclase has been inhibited by an intracellular regulator, the synthesis of which must have been stimulated following the first stimulation with adrenaline. It is unclear up to now, whether homologous and heterologous desensitization on the one hand and activation of inhibitory G-proteins (Gi) on the other are the only mechanisms by which adenylate cyclase activity is regulated (2). In addition to these mechanisms, there also exists a regulator of low molecular weight, which is a potent inhibitor of adenylate cylase (3,4).


Adenylate Cyclase Positive Inotropic Effect Cyclic Phosphate Phosphoprotein Phosphatase Laser Desorption Mass Spectrometry 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    R. J. Ho, J. D. Bomboy, H. K. Wasner, and E. W. Sutherland, Preparation and characterization of a hormone antagonist from adipocytes, in: “Methods in Enzymology”, S.P. Colowick and N.O. Kaplan, eds., vol. 37: 431–438 (1975).Google Scholar
  2. 2.
    D. R. Sibley, J. L. Benovic, M. G. Caron, and R. J. Lefkowitz, Regulation of trans-membrane signaling by receptor phosphorylation, Cell 48: 913–922 (1987).CrossRefPubMedGoogle Scholar
  3. 3.
    H. K. Wasner, On the biochemistry of a new hormone-messenger involving the alpha-receptor in rat liver membrane, Abstr. Commun. 10th Meet. Fed. Eur. Biochem. Soc., no 1367 (1975).Google Scholar
  4. 4.
    H. K. Wasner, Biosynthesis of a cyclic AMP antagonist in hepatocytes from rats after adrenaline-or insulin-stimulation, FEBS Lett. 133: 260–264 (1981).CrossRefPubMedGoogle Scholar
  5. 5.
    H. K. Wasner, and U. Salge, Prostaglandylinositol cyclic phosphate, a second messenger for insulin, in: “Recent Trends in Management of Diabetes Mellitus”, N. Sakamoto, K. G. M. M. Alberti, N. Hotta, eds., Excerpta Medica, Internat. Congress Series, Vol. 726: 226–231 (1987).Google Scholar
  6. 6.
    H. K. Wasner, Regulation of protein kinase and phosphoprotein phosphatase by cAMP and cAMP-antagonist, FEBS Lett. 57: 60–63 (1975).CrossRefPubMedGoogle Scholar
  7. 7.
    H. K. Wasner, Prostaglandylinositol cyclic phosphate, an antagonist to cyclic AMP, in: “Prostaglandins, Leukotrienes and Lipoxins”, J. M. Bailey, ed., Plenum Publishing Corporation, New York, pp. 251–257 (1985).CrossRefGoogle Scholar
  8. 8.
    H. K. Wasner, cAMP antagonist, the hormone messenger of insulin, Akt. Endokrinol. und Stoffwechsel 1: 207–208 (1980).Google Scholar
  9. 9.
    H. K. Wasner, Prostaglandylinositol cyclic phosphate, a second messenger for insulin, Second Int. Symposium on Insulin Receptors (Rome, Italy) p. 33 (1983).Google Scholar
  10. 10.
    D. B. Wilson, T. E. Bross, W. R. Sherman, R. A. Berger and P. W. Majerus, Inositol cyclic phosphates are produced by cleavage of phosphatidylphosphoinositols (polyphosphoinositides) with purified sheep seminal phospholipase C enzymes, Proc. Natl. Acad. Sci. USA 82: 4013–4017 (1985).CrossRefPubMedGoogle Scholar
  11. 11.
    R. Kaufmann, LAMMS in biomedical research: achievements, shortcomings, promises, in: “Microbeam analysis”. P. E. Russell, ed., San Francisco Press, San Francisco, pp. 35–42 (1989).Google Scholar
  12. 12.
    B. Spengler, D. Kirsch, R. Kaufmann, M. Karas, F. Hillenkamp, and U. Giessmann, On the detection of large molecules in matrix assisted UV laser desorption, Rapid Commun. Mass Spectrom. 4: 301–305 (1990).Google Scholar
  13. 13.
    R. H. Michell, Inositolphospholipid in membrane function, TIBS 4: 128–131 (1979).Google Scholar
  14. 14.
    P. J. Marshall, J. F. Dixon and L. E. Hokin, PGE derived from phosphatidylinositol in the exocrine pancreas facilitated secretion by an action on the duct, J. Pharmacol. Exp. Ther. 221: 645–649 (1982).PubMedGoogle Scholar
  15. 15.
    R. M. Burch, A. Luini, D. E. Mais, D. Corda, J. Y. Vanderhoek, L. D. Kohn, and J. Axelrod, al-Adrenergic stimulation of arachidonic acid release and metabolism in rat thyroid cell line, J. Biol. Chem. 261: 11236–11241 (1986).PubMedGoogle Scholar
  16. 16.
    J. E. Pessin, W. Gitomes, Y. Oka, C. L. Oppenheimer and M. P. Czech, ß-Adrenergic regulation of insulin and epidermal growth factor receptors in rat adipocytes, J. Biol. Chem. 258: 7486–7394 (1983).Google Scholar
  17. 17.
    R. H. Strasser, G. L. Stiles and R. J. Lefkowitz, Translocation and uncoupling of the ß-adrenergic receptor in rat lung after catecholamine promoted desensitization in vivo, Endocrinology 115: 1392–1400 (1984).CrossRefPubMedGoogle Scholar
  18. 18.
    H. Lemoine, B. Ehle, and A. J. Kaumann, Direct labelling of ß2 adrenoceptors. Comparison of binding potency of 3H-ICI 118,551 and blocking potency of ICI 118,551. Naunyn-Schmiedeberg’s Arch. Pharmacol. 331: 40–51 (1985).Google Scholar
  19. 19.
    U. Pfeifer, E. Werder and H. Bergeest, Inhibition by insulin of the formation of autophagic vacuoles in rat liver, J. Cell. Biol. 78: 152–165 (1978).CrossRefPubMedGoogle Scholar
  20. 20.
    W. A. Dunn, Jr., Studies on the mechanisms of autophagy: Formation of the autophagic vacuole, J. Cell. Biol. 110: 1923–1933 (1990).CrossRefPubMedGoogle Scholar
  21. 21.
    A. J. Kaumann, and H. Lemoine, ß2 Adrenoceptor-mediated positive inotropic effect of adrenaline in human ventricular myocardium. Quantitative discrepancies with binding and adenylate cyclase stimulation. Naunyn-Schmiedeberg’s Arch. Pharmacol. 335: 403–411 (1987).Google Scholar
  22. 22.
    H. Lemoine, and A. J. Kaumann, Regional differences of Bi-and ß2 adrenoceptormediated functions in feline heart. A ß2 adrenoceptor-mediated positive inotropic effect possibly unrelated to cyclic AMP. Naunyn-Schmiedeberg’s Arch. Pharmacol. (accepted for publication) (1991).Google Scholar
  23. 23.
    R. Bruckner, W. Meyer, A. Mügge, W. Schmitz, and H. Scholz, a-Adrenoceptormediated positive inotropic effect of phenylephrine in isolated human ventricular myocardium. Eur J. Pharmacol. 99: 345–347 (1984).CrossRefPubMedGoogle Scholar
  24. 24.
    M. Endoh, Regulation of myocardial contractility via adrenoceptors: differential mechanisms of a-and ß-adrenoceptor-mediated actions. In: H. Grobecker, A. Philippu, K. Starke, New Aspects of the role of adrenoceptors in the cardiovascular system. Berlin: Springer, 78–105 (1986).CrossRefGoogle Scholar
  25. 25.
    G. L. Stiles, M. G. Caron, and R. J. Lefkowitz, ß-Adrenergic receptors: Biochemical mechanisms of physiological regulation. Physiol. Rev. 64, 2: 661–743 (1984)PubMedGoogle Scholar
  26. 26.
    R. W. Tsien RW, Cyclic AMP and contractile activity in heart. Adv. Cyclic. Nucleotide Res. 8: 363–420 (1977).Google Scholar
  27. 27.
    J. R. Blinks, and M. Endoh, Modification of myofibrillar responsiveness to Cat+ a an inotropic mechanism. Circulation 73 (suppl III): 85–98 (1986).Google Scholar
  28. 28.
    L. O. Buxton, and L. L. Brunton, a-Adrenergic receptors on rat ventricular myocytes: characteristics and linkage to cyclic AMP metabolism. Am. J. Physiol. 251: H307 - H313 (1986).PubMedGoogle Scholar
  29. 29.
    G. A. Robison, R. W. Butcher, and E. W. Sutherland, Adenylate cyclase as an adrenergic receptor. Ann. NY Acad. Sci. 139: 703–723 (1967).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • H. Wasner
    • 1
  • H. Lemoine
    • 2
  • E. Junger
    • 1
  • M. Leßmann
    • 1
  • R. Kaufmann
    • 2
  1. 1.Diabetes-ForschungsinstitutDüsseldorf 1Germany
  2. 2.Institut für Lasermedizin, UniversitätsstraßeUniversität DüsseldorfDüsseldorf 1Germany

Personalised recommendations