Distinction of Receptor from Nonreceptor Interactions in Binding Studies

  • Morley D. Hollenberg
  • Pedro Cuatrecasas
Part of the The Receptors book series (REC, volume 1)


Studies of the binding of ligands to various putative pharmacologic receptors are entering a new phase. Over the past decade, sufficient expertise has been developed to measure with confidence the binding of highly radioactively labeled probes to quantitatively small numbers of high-affinity binding sites, which in most cases represent pharmacologic receptors of interest. Now, these techniques are being employed to study receptors for an ever-burgeoning number of pharmacologically active agents [Cuatrecasas and Hollenberg (1976); collection of reviews edited by Blecher (1976)]. Furthermore, it is becoming apparent that the task of assessing receptor characteristics by ligand binding studies (e.g., receptor changes related to desensitization phenomena) may require a more sophisticated approach than may have been initially considered adequate. It thus appears appropriate to develop an overview for such studies, particularly from the point of view of distinguishing ligand binding sites which typify “true” receptor characteristics (therefore specific binding sites) from those cellular binding sites which do not reflect receptor properties (therefore nonspecific or nonreceptor binding sites).


Human Serum Albumin Ligand Affinity Native Insulin Pharmacologic Receptor Label Ligand 
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. Arunlakshana, O., and Schild, H. O., 1959, Br. J. Pharmacol. 14:48.Google Scholar
  2. Barlow, R. B., and Stephenson, R. P., 1970, in: A Companion to Medical Studies, Vol. 2 (R. Passmore and J. S. Robson, eds.), p. 31, Blackwell’s, Oxford.Google Scholar
  3. Bennett, V., and Cuatrecasas, P., 1976, in: Methods in Receptor Research (M. Blecher, ed.), Part I, p. 73, New York.Google Scholar
  4. Birdsall, N. J. M., and Hulme, E. C., 1976, J. Neurochem. 27:7.PubMedCrossRefGoogle Scholar
  5. Blecher, M. (ed.), 1976, Methods in Receptor Research, Parts I and II, Dekker, New York.Google Scholar
  6. Buller, R. F., Schrader, W. T., and O’Malley, B., 1976, J. Steroid Biochem. 7:321.PubMedCrossRefGoogle Scholar
  7. Carpenter, G., Lembach, K. J., Morrison, M. M., and Cohen, S., 1975, J. Biol. Chem. 250:4297.PubMedGoogle Scholar
  8. Chang, K. J., Jacobs, S., and Cuatrecasas, P., 1975, Biochim. Biophys. Acta 406:294.PubMedCrossRefGoogle Scholar
  9. Changeux, J.-P., 1966, Mol. Pharmacol. 2:369.PubMedGoogle Scholar
  10. Changeux, J.-P., and Podleski, T. R., 1968, Proc. Natl. Acad. Sci. USA 59:944.PubMedCrossRefGoogle Scholar
  11. Changeux, J.-P., Blumenthal, R., Kasai, M., and Podleski, T., 1970, in: Molecular Properties of Drug Receptors (R. Porter and M. O’Connor, eds.), p. 197, Churchill, London.Google Scholar
  12. Cheng, Y.-C., and Prusoff, W. H., 1973, Biochem. Pharmacol. 22:3099.PubMedCrossRefGoogle Scholar
  13. Clark, A. J., 1926a, J. Physiol. 61:530.Google Scholar
  14. Clark, A. J., 1926b, J. Physiol. 61:547.Google Scholar
  15. Cohen, J. B., and Changeux, J.-P., 1975, Ann. Rev. Pharmacol. 15:83.PubMedCrossRefGoogle Scholar
  16. Colquhoun, D., 1973, in: Drug Receptors (H. P. Rang, ed.), p. 149, Butterworth’s, London.Google Scholar
  17. Creese, I., Burt, D. R., and Snyder, S. H., 1975, Life Sci. 17:993.CrossRefGoogle Scholar
  18. Cuatrecasas, P., 1971, Proc. Natl. Acad. Sci. USA 68:1264.PubMedCrossRefGoogle Scholar
  19. Cuatrecasas, P., 1973, Biochemistry 12:3547.PubMedCrossRefGoogle Scholar
  20. Cuatrecasas, P., 1974, Annu. Rev. Biochem. 43:169.PubMedCrossRefGoogle Scholar
  21. Cuatrecasas, P., and Hollenberg, M. D., 1975, Biochem. Biophys. Res. Commun. 62:31.PubMedCrossRefGoogle Scholar
  22. Cuatrecasas, P., and Hollenberg, M. D., 1976, Adv. Protein Chem. 30:251.PubMedCrossRefGoogle Scholar
  23. Cuatrecasas, P., Tell, G. P. E., Sica, V., Parikh, I., and Chang, K.-J., 1974, Nature (London) 247:92.CrossRefGoogle Scholar
  24. Cuatrecasas, P., Hollenberg, M. D., Chang, K.-J., and Bennett, V., 1975, Recent Prog. Horm. Res. 31:37.PubMedGoogle Scholar
  25. De Meyts, P., 1976, in: Methods in Receptor Research (M. Blecher, ed.), Part I, Chap. 11, Dekker, New York.Google Scholar
  26. Edelstein, S. J., 1972, Biochem. Biophys. Res. Commun. 48:1160.PubMedCrossRefGoogle Scholar
  27. Ehrlich, P., 1956, Nobel lecture, 1908, in: The Collected Papers of P. Ehrlich, Vol. Ill (F. Himmelweit, M. Marquardt, and H. Dale, eds.), p. 183, Pergamon Press, Elmsford, N.Y.Google Scholar
  28. Freychet, P., Roth, J., and Neville, D. M., 1971a, Proc. Natl. Acad. Sci. USA 68:1833.CrossRefGoogle Scholar
  29. Freychet, P., Roth, J., and Neville, D. M., 1971b, Biochem. Biophys. Res. Commun. 43:400.CrossRefGoogle Scholar
  30. Gill, E. W., and Rang, H. P., 1966, Mol. Pharmacol 2:284.PubMedGoogle Scholar
  31. Gliemann, J., Gammeltoft, S., and Vinten, J., 1975, J. Biol. Chem. 250:3368.PubMedGoogle Scholar
  32. Goldstein, A., Aronow, L., and Kaiman, S. M., 1974, Principles of Drug Action, Wiley, New York.Google Scholar
  33. Gupta, S. K., Moran, J. F., and Triggle, D. J., 1976, Mol. Pharmacol. 13:1019.Google Scholar
  34. Hall, Z. W., 1972, Annu. Rev. Biochem. 41:925.PubMedCrossRefGoogle Scholar
  35. Hollenberg, M. D., 1975, Arch. Biochem. Biophys. 171:371.PubMedCrossRefGoogle Scholar
  36. Hollenberg, M. D., and Cuatrecasas, P., 1975, in: Biochemical Actions of Hormones, Vol. III (G. Litwack, ed.), p. 41, Academic Press, New York.Google Scholar
  37. Hollenberg, M. D., and Gregory, H., 1978, Mol. Pharmacol., submitted.Google Scholar
  38. Horn, H. S., 1975, in: Handbook of Psychopharmacology, Vol. 2 (L. L. Iversen, S. D. Iversen, and S. H. Snyder, eds.), p. 129, Plenum Press, New York.Google Scholar
  39. Jacobs, S., and Cuatrecasas, P., 1976, Biochim. Biophys. Acta 433:482.PubMedCrossRefGoogle Scholar
  40. Jacobs, S., Chang, K.-J., and Cuatrecasas, P., 1975, Biochem. Biophys. Res. Commun. 66:687.PubMedCrossRefGoogle Scholar
  41. Karlin, A., 1967, J. Theor. Biol 16:306.PubMedCrossRefGoogle Scholar
  42. Langley, J. N., 1906, Proc. Roy. Soc. London Ser. B 78:170.CrossRefGoogle Scholar
  43. Lefkowitz, R. J., Limbird, L. E., Mukherjee, C., and Caron, M. G., 1976, Biochim. Biophys. Acta 457:1.PubMedCrossRefGoogle Scholar
  44. Loh, H. H., Cho, T. M., Wu, Y. C., and Way, E. L., 1974, Life Sci. 14:2231.PubMedCrossRefGoogle Scholar
  45. McGhee, J. D., and von Hippel, P. H., 1974, J. Mol. Biol. 86:469.PubMedCrossRefGoogle Scholar
  46. Paton, W. D. M., 1961, Proc. Roy. Soc. London Ser. B 154:21.CrossRefGoogle Scholar
  47. Paton, W. D. M., and Rang, H. P., 1965, Proc. Roy. Soc. London Ser. B 163:1.CrossRefGoogle Scholar
  48. Phillips, J. L., 1976, Biochem. Biophys. Res. Commun. 71:726.PubMedCrossRefGoogle Scholar
  49. Rodbard, D., 1973, in: Receptors for Reproductive Hormones (B. W. O’Malley, and A. R. Means, eds.), p. 289, Plenum Press, New York.CrossRefGoogle Scholar
  50. Scatchard, G., 1949, Ann. NY Acad. Sci. 51:660.CrossRefGoogle Scholar
  51. Schild, H. O., 1949, Br. J. Pharmacol. 4:277.Google Scholar
  52. Segel, I. H., 1975, Enzyme Kinetics, Wiley, New York.Google Scholar
  53. Snyder, S. H., 1975, Biochem. Pharmacol. 24:1371.CrossRefGoogle Scholar
  54. Snyder, S. H., Pasternak, G. W., and Pert, C. B., 1975, in: Handbook of Psychopharmacology, Vol. 5 (L. L. Iversen, S. D. Iversen, and S. H. Snyder, eds.), p. 329, Plenum Press, New York.Google Scholar
  55. Spelsberg, T. C., Pikier, G. M., and Webster, R. A., 1976, Science 194:197.PubMedCrossRefGoogle Scholar
  56. Stephenson, R. P., 1956, Br. J. Pharmacol. 11:379.Google Scholar
  57. Straus, O. H., and Goldstein, A. J., 1943, J. Gen. Physiol. 26:559.PubMedCrossRefGoogle Scholar
  58. Sudlow, G., Birkett, D. J., and Wade, D. N., 1976, Mol. Pharmacol. 12:1052.PubMedGoogle Scholar
  59. U’Prichard, D. C., and Snyder, S. H., 1977, Life Sci. 20:527.PubMedCrossRefGoogle Scholar
  60. Waud, D. R., 1968, Pharmacol. Rev. 20:49.PubMedGoogle Scholar
  61. Webb, J. L., 1963, Enzyme and Metabolic Inhibitors, Vol. 1, Academic Press, New York.Google Scholar
  62. Yamamura, H., and Snyder, S. H., 1974, Proc. Natl. Acad. Sci. USA 71:1725.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • Morley D. Hollenberg
    • 1
  • Pedro Cuatrecasas
    • 2
  1. 1.Division of Clinical Pharmacology, Departments of Medicine and of Pharmacology and Experimental TherapeuticsThe Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.The Wellcome Research LaboratoriesBurroughs Wellcome CompanyResearch Triangle ParkUSA

Personalised recommendations