Beta-Adrenergic Stimulation of Adenylate Cyclase and Alpha-Adrenergic Inhibition of Adenylate Cyclase: GTP-Binding Proteins as Macromolecular Messengers

  • Lee E. Limbird
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 161)


This review, which is a summary of an oral presentation made at the International Study Group for Research in Cardiac Metabolism, is a brief synopsis of work in our laboratory concerning the mechanism of hormonal regulation of adenylate cyclase. By its very nature, it refers almost entirely to our own work. However, since a number of laboratories have contributed to the field in ways at least as significant as our own, I recommend reading the reviews cited as references 4, 7 and 11 for a more comprehensive summary of the literature. The emphasis of this review is the role of GTP-binding proteins as important communicators between hormone-occupied receptors and the catalytic subunit of adenylate cyclase. The experimental work summarized emphasizes the extent to which one can determine the “intactness” receptor-effector coupling by focusing on receptor-agonist interactions, and modulation of these interactions by guanine nucleotides.


Adenylate Cyclase Cholera Toxin Guanine Nucleotide Adenylate Cyclase Activity Large Molecular Size 
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  1. 1.
    Cassel, D. and Selinger, Z. Catecholamine-Stimulated GTPase Activity in Turkey Erythrocyte Membranes. Biochim. Biophys Acta 452, 538–551 (1976).PubMedGoogle Scholar
  2. 2.
    Cassel, D., Levkovitz, H. and Selinger, S. The Regulatory GTPase Cycle of Turkey Erythrocyte Adenylate Cyclase. J. Cycl. Nucl. Res. 3, 393–406, 1977.Google Scholar
  3. 3.
    Cassel, D. and Selinger, Z. Mechanism of Adenylate .Cyclase Activation Through the β-Adrenergic Receptor: Catecholamine-induced Displacement of Bound GDP by GTP. Proc. Natl. Acad. Sci. USA 75, 4155–4159, 1978.PubMedCrossRefGoogle Scholar
  4. 4.
    Cooper, D.M.F. Bimodal Regulation of Adenylate Cyclase. FEBS Lett. 138, 157–163, 1982.PubMedCrossRefGoogle Scholar
  5. 5.
    DeLean, A., Stadel, J.M. and Lefkowitz, R.J. A Ternary Complex Explains the Agonist-specific Binding Properties of the Adenylate Cyclase-coupled β-Adrenergic Receptor. J. Biol. Chem. 255, 7108–7117, 1980.Google Scholar
  6. 6.
    Gill, D.M. and Meren, R. ADP-ribosylation of Membrane Proteins Catalyzed by Cholera Toxin: Basis of the Activation of Adenylate Cyclase. Proc. Natl. Acad. Sci. USA 75, 3050–3054, 1978.PubMedCrossRefGoogle Scholar
  7. 7.
    Gilman, A.G. and Ross, E.M. Biochemical Properties of Hormonesensitive Adenylate Cyclase. Ann. Rev. Biochem. 49, 533–564, 1980.PubMedCrossRefGoogle Scholar
  8. 8.
    Limbird, L.E. and Lefkowitz, R.J. Agonist-induced Increase in Apparent β-Adrenergic Receptor Size. Proc. Natl. Acad. Sci. USA 75, 228–232, 1978.PubMedCrossRefGoogle Scholar
  9. 9.
    Limbird, L.E., Gill, D.M., Stadel, J.M., Hickey, A.R. and Lefkowitz, R.J. Loss of β-Adrenergic Receptor-Guanine Nucleotide Regulatory Protein Interactions Accompanies Decline in Catecholamine Responsiveness of Adenylate Cyclase in Maturing Rat Erythrocytes. J. Biol. Chem. 255, 1854–1861, 1980.PubMedGoogle Scholar
  10. 10.
    Limbird, L.E., Gill, D.M. and Lefkowitz, R.J. Agonist-promoted Coupling of the β-Adrenergic Receptor with the Guanine Nucleotide Regulatory Protein of the Adenylate Cyclase System. Proc. Natl. Acad. Sci. 77, 775–779, 1980.PubMedCrossRefGoogle Scholar
  11. 11.
    Limbird, L.E. Activation and Attenuation of Adenylate Cyclase (Review Article) Biochem. J. 195, 1–13, 1981.PubMedGoogle Scholar
  12. 12.
    Pfeuffer, T. Guanine-nucleotide-controlled Interactions Between Components of Adenylate Cyclase. FEBS Lett. 101, 85–89, 1979.PubMedCrossRefGoogle Scholar
  13. 13.
    Smith, S.K. and Limbird, L.E. Solubilization of Human Platelet α -Adrenergic Receptors: Evidence that Agonist Occupancy of the Receptor Stabilizes Receptor-Effector Interactions. Proc. Natl. Acad. Sci. 78, 4026–4030, 1981.PubMedCrossRefGoogle Scholar
  14. 14.
    Smith, S.K. and Limbird, L.E. Evidence That Human Platelet α -Adrenergic Receptors Coupled to Inhibition of Adenylate Cyclase are not Associated with the Subunit of Adenylate Cyclase ADP-ribosylated by Cholera Toxin. J. Biol. Chem. In Press, Sept./Oct., 1982.Google Scholar
  15. 15.
    Stadel, J.M., Schorr, R.G.L., Limbird, L.E. and Lefkowitz, R.J. Evidence That a β -Adrenergic Receptor-associated Guanine Nucleotide Regulatory Protein Conveys Guanosine 5’-0-(3-thiotriphosphate)-dependent Adenylate Cyclase Activity. J. Biol. Chem. 256, 8718–8723, 1981.PubMedGoogle Scholar
  16. 16.
    Williams, L.T. and Lefkowitz, R.J. Slowly Reversible Binding of Catecholamine to a Nucleotide-Sensitive State of the β -Adrenergic Receptor. J. Biol. Chem. 252, 7207–7213, 1977.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Lee E. Limbird
    • 1
  1. 1.Dept. of PharmacologyNashvilleUSA

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