Analysis of Binding Data

  • Edward C. Hulme
Part of the Methods in Molecular Biology book series (MIMB, volume 106)

Abstract

A receptor is an allosteric macromolecule (usually associated with a particular cell type) that binds a specific chemical substance (usually secreted by another cell) and in the process undergoes a defined conformational change that triggers a series of biochemical and physiological events within the target cell.

References

  1. 1.
    Hulme, E. C. and Birdsall, N. J. M. (1992) Strategy and tactics in receptor-bind ing studies, in Receptor-Ligand Interactions, A Practical Approach (Hulme, E. C., ed.) IRL, Oxford, U.K., pp. 63–176.Google Scholar
  2. 2.
    Samama, P., Cotecchia, S., Costa, T., and Lefkowitz, R. J. (1993) A mutation-induced activated state of the β2-adrenergic receptor: Extending the ternary complex model. J. Biol. Chem. 268, 4625–4636.PubMedGoogle Scholar
  3. 3.
    Lazareno, S. and Birdsall, N. J. M. (1995) Detection, quantitation and verification of allosteric interactions of agents with labelled and unlabelled ligands at G protein-coupled receptors: Interactions of strychnine and acetylcholine at muscarinic receptors. Mol. Pharmacol. 48, 362–378.PubMedGoogle Scholar
  4. 4.
    Birdsall, N. J. M., Farries, T., Gharagozloo, P., Kobayashi, S., Kuonen, D., Lazareno, S., et al. (1997) Selective allosteric enhancement of the binding and actions of acetylcholine at muscarinic receptor subtypes. Life Sci. 60, 1047–1052.PubMedCrossRefGoogle Scholar
  5. 5.
    Onaran, H. O., Costa, T., and Rodbard, D. (1992) βγ subunits of guanine nucleotide binding proteins and regulation of spontaneous receptor activity: Thermodynamic model for the interaction between receptors and guanine nucleotide-binding protein subunits. Mol. Pharmacol. 43, 245–256.Google Scholar
  6. 6.
    Wells, J. W. W. (1992) Analysis and interpretation of binding at equilibrium, in Receptor-Ligand Interactions, A Practical Approach (Hulme, E. C., ed.) IRL, Oxford, U.K.Google Scholar
  7. 7.
    Prinz, H. and Maelicke, A. (1992) Ligand binding to the membrane-bound acetylcholine receptor from Torpedo marmorata: a complete mathematical analysis. Biochem. 31, 6728–6738.CrossRefGoogle Scholar
  8. 8.
    Lemmon, M. A. and Schlessinger, J. (1994) Regulation of signal transduction and signal diversity by receptor oligomerization. Trends Biochem. Sci. 19, 459–463.PubMedCrossRefGoogle Scholar
  9. 9.
    Costa, T., Ogino, Y., Munson, P. J., Onaran, H. O., and Rodbard, D. (1992) Drug efficacy at guanine nucleotide-binding regulatory protein-linked receptors: thermodynamic interpretation of negative antagonism and of receptor activity in the absence of ligand. Mol. Pharmacol. 41, 549–560.PubMedGoogle Scholar
  10. 10.
    Wreggett, K. A. and Wells, J. W. (1995) Cooperativity manifest in the binding properties of purified cardiac muscarinic receptors. J. Biol. Chem. 270, 22,488–22,499.PubMedCrossRefGoogle Scholar
  11. 11.
    Neubig, R. R. (1994) Membrane organisation in G protein mechanisms. FASEB J. 8, 939–946.PubMedGoogle Scholar
  12. 12.
    Hebert, T. E., Moffet, S., Morello, J. P., Loisel, T. P., Bichet, D. G., Barrett, C, and Bouvier, M. (1996) A peptide derived from a β2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J. Biol. Chem. 271, 16,384–16,392.PubMedCrossRefGoogle Scholar
  13. 13.
    Hirschberg, B. T. and Schimerlik, M. I. (1994) A kinetic model for oxotremorine M binding to recombinant porcine m2 muscarinic receptors expressed in Chinese hamster ovary cells. J. Biol. Chem. 269, 26,127–26,135.PubMedGoogle Scholar
  14. 14.
    Maggio, R., Barbier, P., Fornai, F., and Corsini, G. U. (1996) Functional role of the third cytoplasmic loop in muscarinic receptor dimerization. J. Biol. Chem. 271, 31,055–31,060.PubMedCrossRefGoogle Scholar
  15. 15.
    Lazareno, S., Farries, T., and Birdsall, N. J. M. (1993) Pharmacological characterisation of guanine nucleotide exchange reactions in membranes from CHO cells stably transfected with human muscarinic receptors M1–M4. Life Sci. 52, 449–456.PubMedCrossRefGoogle Scholar
  16. 16.
    Lazareno, S. and Birdsall, N. J. M. (1993) Pharmacological characterization of acetylcholine-stimulated [35S]GTPγS binding mediated by human muscarinic m1–m4 receptors: antagonist studies. Br. J. Pharmacol. 109, 1120–1127.PubMedGoogle Scholar
  17. 17.
    Cheng, Y. C. and Prusoff, W. H. (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem. Pharmacol. 22, 3099–3108.PubMedCrossRefGoogle Scholar
  18. 18.
    Mosteller, F. and Tukey, J. W. (1977) Data Analysis and Regression, Addison-Wesley, Reading, MA.Google Scholar
  19. 19.
    Leatherbarrow, R. J. (1992) GraFit Version 3.0, Erithacus Software Ltd., Staines, U.K.Google Scholar
  20. 20.
    Munson, P. J. and Rodbard, D. (1980) LIGAND: a versatile computerised approach for characterization of ligand-binding systems. Anal. Biochem. 107, 220–239.PubMedCrossRefGoogle Scholar
  21. 21.
    Bowen, W. P. and Jerman, J. C. (1995) Nonlinear regression using spreadsheets. Trends Pharmacol. Sci. 16, 413–417.PubMedCrossRefGoogle Scholar
  22. 22.
    Page, K. M., Curtis, C. A. M., Jones, P. G., and Hulme, E. C. (1995) The functional role of the binding site aspartate in muscarinic acetylcholine receptors, probed by site-directed mutagenesis. Eur. J. Mol. Pharmacol. 289, 429–437.CrossRefGoogle Scholar
  23. 23.
    Lu, Z.-L., Curtis, C. A., Jones, P. G., Pavia, J., and Hulme, E. C. (1996) The role of the aspartate-arginine-tyrosine triad in the ml muscarinic receptor: mutations of aspartate 122 and tyrosine 124 decrease receptor expression but do not abolish signalling. Mol. Pharmacol. 51, 234–241.Google Scholar
  24. 24.
    Wells, J. W., Birdsall, N. J. M., Burgen, A. S. V., and Hulme, E. C. (1980) Competitive binding studies with multiple sites: effects arising from depletion of the free radioligand. Biochim. Biophys. Ada 632, 464–469.CrossRefGoogle Scholar
  25. 25.
    Goldstein, A. and Barrett, R. W. (1987) Ligand dissociation constants from competition binding assays—errors associated with ligand depletion. Mol. Pharmacol. 31, 603–609.PubMedGoogle Scholar
  26. 26.
    Schuck, P. and Minton, A. P. (1996) Kinetic analysis of biosensor data: elementary tests for self-consistency. Trends Biochem. Sci. 21, 458–460.PubMedCrossRefGoogle Scholar
  27. 27.
    Birdsall, N. J. M., Burgen, A. S. V., Hulme, E. C., Stockton, J. M., and Zigmond, M. J. (1983) The effect of McN-A-343 on muscarinic receptors in the cerebral cortex and heart. Br. J. Pharmacol. 78, 257–259.PubMedGoogle Scholar
  28. 28.
    Swillens, S., Waelbroeck, M., and Champeil, P. (1995) Does a radiolabelled ligand bind to a homogeneous population of non-interacting receptor sites? Trends Pharmacol. Sci. 16, 151–155.PubMedCrossRefGoogle Scholar
  29. 29.
    Segel, I. H. (1994) The effects of labeled and unlabeled impurities on the analysis of equilibrium binding and initial velocity data by means of Scatchard plots. J. Theoret. Biol. 171, 267–280.CrossRefGoogle Scholar
  30. 30.
    Cohen, F. R., Lazareno, S., and Birdsall, N. J. M. (1996) The affinity of adenosine for the high-and low-affinity states of the human adenosine Al receptor. Eur. J. Pharmacol. 309, 111–114.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 1999

Authors and Affiliations

  • Edward C. Hulme
    • 1
  1. 1.Division of Physical BiochemistryNational Institute for Medical ResearchLondonUK

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