Spermine Inhibition of Basal and Stimulated Adenylate Cyclase is Mediated by the Inhibitory GTP-Binding Protein (Gi)

  • Carlo Clo
  • Benedetta Tantini
  • Pietro Sacchi
  • Claudio M. Caldarera
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 250)


In the past few years, substantial evidence has accumulated suggesting that a family of heterotrimeric (α, β, γ-subunits) guanine nucleotide binding proteins (G-proteins) may mediate a number of transmembrane signaling events. These include regulation of membrane-bound adenylate cyclaseV1, 2, 3, 4, the breakdown of phosphatidylinositol biphosphate by phospholipase C,5 the activation of cGMP-phosphodiesterase by rhodopsin6 and the conductance of some ionic (K+, Ca2+) channels7. Recent evidence also suggests that G-proteins may be regulated by phosphorylation by protein kinase C8 and the insulin receptor tyrosyl kinase.9


Adenylate Cyclase Guanine Nucleotide Pertussis Toxin Adenylate Cyclase Activity Guanine Nucleotide Binding Protein 
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  1. 1.
    L. E. Limbird, Activation and attenuation of adenylate cycla-se, Biochem. J. 195: 1 (1981).PubMedGoogle Scholar
  2. 2.
    A. G. Gilam, G proteins and dual control of adenylate cyclase, Cell 36: 577 (1984).CrossRefGoogle Scholar
  3. 3.
    L. Birnbaumer, J. Codina, R. Mattera, R.A. Cerione, J.D. Hildebrandt, T. Sunyer, F. J. Rojas, M. G. Caron, R. J. Lefkowitz and R. Iyengar, Regulation of hormone receptors and adenylate cyclases by guanine nucleotide binding N proteins, in: “Recent Progress in Hormone Research”, R. O. Greep, ed., Academic Press, New York, 41: 41 (1985).Google Scholar
  4. 4.
    A. Levitzki, Regulation of adenylate cyclase by hormones and G-proteins, FEBS Lett. 211: 113 (1987).PubMedCrossRefGoogle Scholar
  5. 5.
    A.P. Dowson, GTP enhances inositol triphosphate-stimulated Ca2+ release from rat liver microsomes, FEBS Lett.185: 147 (1985).CrossRefGoogle Scholar
  6. 6.
    L. Stryer, G proteins: a family of signal transducers, Ann. Rev. Cell. Biol. 2: 391 (1986).PubMedCrossRefGoogle Scholar
  7. 7.
    M. D. Houslay, Ion channels controlled by guanine nucleotide regulatory proteins, Trends Biochem.Sci.12: 167 (1987).Google Scholar
  8. 8.
    T. Katada, A. G. Gilman, Y. Watanabe, S. Bauer, and K. H. Jakobs, Protein kinase C phosphorylates the inhibitory guanine nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase, Eur.J.Biochem. 151: 431 (1985).PubMedCrossRefGoogle Scholar
  9. 9.
    R.M. O’Brein, M.D. Houslay, G.M. Milligan, and D. Siddle, The insulin receptor tyrosyl kinase phosphorilates holomeric forms of the guanine nucleotide regulatory proteins Gi and Go, FEBS Lett. 212: 281 (1987).CrossRefGoogle Scholar
  10. 10.
    T. Higashijima, K. M. Ferguson, P. C. Sternweis, M.D. Smigel, and A.G. Gilman, Effects of Mg[su2+ and the ßγ-submit complex on the interactions of guanine nucleotide with G protein, J. Biol.Chem. 262: 762 (1987).PubMedGoogle Scholar
  11. 11.
    J. Codina, J. D. Hildebrandt, L. Birnbaumer, and R.D. Sekura, Effects of guanine nucleotides and Mg on human erythrocyte Ni and Ns, the regulatory components of adenylate cyclase, J. Biol. Chem. 259: 11408 (1984).PubMedGoogle Scholar
  12. 12.
    K. H. Jakobs, U. Gehring, B. Gaugler, T. Pfeuffer, and G. Schults, Occurence of an inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase system in cyc variants of S49 lymphoma cells, Eur. J. Biochem. 130: 605 (1983).PubMedCrossRefGoogle Scholar
  13. 13.
    D. C. Lehotay, H. K. Lo, and G. S. Levey, Activation of adenylate cyclase: requirement for phospholipids, in: “Cyclic 3’: 5’ Nucleotides: Mechanism of Action”, H. Cramer and J. Schultz, eds., John Wiley & Sons, London, pp.1 (1977).Google Scholar
  14. 14.
    C. Clo, C. Pignatti, S. Manfroni, S. Marmiroli, and B. Tantini, Modulation of membrane bound adenylate cyclase by polyami-nes, in: “Biomedical Studies of Natural Polyamines”, CM. Caldarera, C. Clo and C. Guarnieri, eds., CLUEB, Bologna, pp. 117 (1986).Google Scholar
  15. 15.
    B. Tadolini, L. Cabrini, L. Landi, E. Varani, and P. Pasquali, Po-lyamine binding to phospholipid vescicles and inhibition of lipid peroxidation, Biochem.Biophys. Res. Commun. 122: 550 (1984).PubMedCrossRefGoogle Scholar
  16. 16.
    C. Clo, B. Tantini, M.N. Coccolini, and C. M. Caldarera, Mediation of polyamine-induced decrease of cAMP content by cAMP-phosphodiesterase in chick embryo heart cell cultures, J.Mol.Cell.Cardiol. 13: 773 (1981).PubMedCrossRefGoogle Scholar
  17. 17.
    M.H. Bradford, A rapid and sensitive method for the quanti-tation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal.Biochem. 72: 248 (1976).PubMedCrossRefGoogle Scholar
  18. 18.
    K. B. Seamon, and J. W. Daly, Guanosine 5’-(ß, γ-imido)triphospha-te inhibition of forskolin-activated adenylate cyclase is mediated by the putative inhibitory guanine nucleotide regulatory protein, J. Biol. Chem. 257: 11591 (1982).PubMedGoogle Scholar
  19. 19.
    K. H. Jakobs, K. Aktories, and G. Schultz, Mechanism of per-tussintoxin action on the adenylate cyclase system, Eur. J. Biochem. 140: 177 (1984).PubMedCrossRefGoogle Scholar
  20. 20.
    P.A. Insel, D. Stengel, N. Ferry, and J. Honoune, Regulation of adenylate cyclase of human platelet membranes by forskolin, J. Biol. Chem. 257: 7485 (1982).PubMedGoogle Scholar
  21. 21.
    T. H. Hudson and J. N. Fain, Forskolin-activated adenylate cyclase, J. Biol. Chem. 258:9755 (1983).PubMedGoogle Scholar
  22. 22.
    L. R. Forte, D. B. Bylund,and W. L. Zahler, Forskolin does not activate sperm adenylate cyclase, Mol.Pharmacol. 24:42 (1983)PubMedGoogle Scholar
  23. 23.
    R. B. Clark, T. J. Goka, D. A. Green, R. Barber, and R. W. Butcher, Differences in the forskolin activation of adenylate cyclase in wild-type and variant lymphoma cells, Mol. Pharmacol. 22:609 (1982).PubMedGoogle Scholar
  24. 24.
    J. D. Hildebrandt and L. Birnbaumer, Inhibitory regulation of adenylyl cyclase in the absence of stimulatory regulation. J. Biol. Chem. 258:13141 (1983).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Carlo Clo
    • 1
  • Benedetta Tantini
    • 1
    • 2
  • Pietro Sacchi
    • 1
  • Claudio M. Caldarera
    • 1
  1. 1.Dipartimento di Biochimica, Centro Studi e Ricerche sul Metabolismo CardiacoUniversità di BolognaItaly
  2. 2.Istituto di CitomorfologiaC.N.R.BolognaItaly

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