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Characterization of the β-Adrenergic Receptor and the Regulatory Control of Adenylate Cyclase

  • Alexander Levitzki
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 11)

Abstract

Numerous tissues possess β-adrenergic receptors coupled to adenylate cyclase. The binding of 1 -catecholamines to the β-adrenergic receptor is specific, rapid and reversible (5, 16). The extent of receptor occupancy is controlled by the expression
$$ \rm K_D=\ \ {(R)\ \ (H)\over (RH)}\\1 $$
([1])
where KD is the receptor-hormone dissociation constant, (R) the concentration of free receptor, (H)the concentration of free hormone and (RH)the concentration of the receptor-hormone complex. The affinity of 1 -catecholamines to the β-receptor as measured by the dose response curve of adenylate cyclase is between 5 × 10−7 M to 10−5 M depending on the activating 1-catecholamine ligand. Since the receptor concentration accessible experimentally rarely exceeds 5 × 10−9 m, attempts to probe the β-receptor by measuring 3H-catacholamine binding were bound to be unsuccessful (6–8). Indeed, it was demonstrated that the ligand binding specificity did not match the specificity of theβ-receptor as defined pharmacologically and biochemically (3, 4). Recent experiments (4, 9) have indeed shown that most of the binding signal is due to non-specific catecholamine binding to non-receptor binding sites. Therefore it became necessary to develop a reliable binding assay for the purpose of direct measurement of ligand binding to the receptor. Such an assay was first developed using 3H-pro-pranolol as the probing ligand (9).

Keywords

Adenylate Cyclase Adenylate Cyclase Activity Receptor Concentration cAMP Formation Ghost Membrane 
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.

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References

  1. 1.
    ATLAS, D., STEER, M. L. and LEVITZKI, A., Proc. Nat. Acad. Sci. USA 71 (1974) 4246.PubMedCrossRefGoogle Scholar
  2. 2.
    AURBACH, G. D., FEDAK, S. A., WOODWARD, C. J., PALMER, J. S., MAUSER, D. and TROXLER, F., Science 186 (1974) 1223.PubMedCrossRefGoogle Scholar
  3. 3.
    CUATRECASAS, P., Ann. Rev. Biochem. 43 (1974)169.PubMedCrossRefGoogle Scholar
  4. 4.
    CUATRECASAS, P., TELL, G. P. E., SICA, V. and PARIKH, I., Nature 247 (1974) 92.PubMedCrossRefGoogle Scholar
  5. 5.
    FURCHGOTT, R. F.,in Handbook of Experimental Pharmacology 33: Catecholamines (H. Blaschko and E. Muscholl eds.) Springer Verlag, New York, (1972) 283.Google Scholar
  6. 6.
    LEFKOWITZ, R. J., N. Eng. J. Med. 288 (1973) 1061.CrossRefGoogle Scholar
  7. 7.
    LEFKOWITZ, R. J., HABER, E. and O’HARA, D., Proc. Nat. Acad. Sci. USA 69 (1972) 2828.PubMedCrossRefGoogle Scholar
  8. 8.
    LEFKOWITZ, R. J. , SHARP, G. W. G. and HABER, E., J. Biol. Chem. 284 (1973) 342.Google Scholar
  9. 9.
    LEVITZKI, A., ATLAS, D. and STEER, M. L., Proc. Nat. Acad. Sci. USA 71 (1974) 2773.PubMedCrossRefGoogle Scholar
  10. 10.
    LEVITZKI, A., SEVILLA, N., ATLAS, D. and STEER, M. L., J. Biol. Chem. (1975) in press.Google Scholar
  11. 11.
    LEVITZKI, A., SEVILLA, N. and STEER, M. L., J. Supramolec. Structure (1975) in press.Google Scholar
  12. 12.
    LIN, M. C, SALOMON, Y., RENDELL, M. and RODBELL, M., J. Biol. Chem. 250 (1975) 4246.PubMedGoogle Scholar
  13. 13.
    LONDOS, C, SALOMON, Y. , LIN, M. C, HARWOOD, J. P., SCHRAMM, M., WOLFF, J. and RODBELL, M., Proc. Nat. Acad. Sci. USA 71 (1974) 3087.PubMedCrossRefGoogle Scholar
  14. 14.
    PFEUFFER, T. and HELMREICH, E. J. M., J. Biol. Chem. 250 (1975) 867.PubMedGoogle Scholar
  15. 15.
    RENDELL, M. , SALOMON, Y., LIN, M. C., RODBELL, M. and BERMAN, M. , J. Biol. Chem. 250 (1975) 4253.PubMedGoogle Scholar
  16. 16.
    ROBINSON, G. A., BUTCHER, R. W. and SUTHERLAND, E. W., Cyclic AMP, Academic Press, New York (1971).Google Scholar
  17. 17.
    RODBELL, M., BIRNBAUMER, L., POHL, S. L. and KRANS, H. M. J., J. Biol. Chem. 246 (1971) 1877.PubMedGoogle Scholar
  18. 18.
    RODBELL, M., LIN, M. C. and SALOMON, Y., J. Biol. Chem. 249 (1974) 59.PubMedGoogle Scholar
  19. 19.
    RODBELL, M., KRANS, H. M. J., POHL, S. L. and BIRNBAUMER, L., J. Biol. Chem. 246 (1971) 1872.PubMedGoogle Scholar
  20. 20.
    SALOMON, Y., LIN, M. C, LONDOS, C, RENDELL, M. and RODBELL, M., J. Biol. Chem. 250 (1975) 4233.Google Scholar
  21. 21.
    SCHRAMM, M. and RODBELL, M., J. Biol. Chem. 250 (1975) 2232.PubMedGoogle Scholar
  22. 22.
    SPIEGEL, A. M. and AURBACH, G. D., J. Biol. Chem. 249 (1974) 7630.PubMedGoogle Scholar
  23. 23.
    STEER, M. L. and LEVITZKI, A., J. Biol. Chem. 250 (1975) 2080.PubMedGoogle Scholar
  24. 24.
    STEER, M. L. and LEVITZKI, A., Arch. Biochem. Biophys. 167 (1975) 371.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • Alexander Levitzki
    • 1
  1. 1.Department of Biological ChemistryThe Hebrew University of JerusalemJerusalemIsrael

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