Abstract
The methods for acquisition and initial analysis of radioligand binding phenomena were summarized in chapter 3. It was demonstrated that equations for linear transformations of binding data were derived assuming that a reversible bimolecular reaction occurred between ligand and receptor and that this interaction obeyed mass action law, namely *D + R ⇌ *DR. Consequently, when data transformations such as the Scatchard plot are nonlinear, when Hill coefficients (nH) do not equal 1.0, or when competition binding curves are not of normal steepness, additional complexities are suggested. Chapter 3 also provided guidelines for evaluating whether or not technical artifacts were responsible for departure of the data from that expected for a simple bimolecular reaction. Once technical artifacts have been excluded, complex binding phenomena suggest the existence of biological complexities which may provide insights into the molecular basis of receptor function.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
General
DeLean, A., Hancock, A.A. and Lefkowitz, R.J. (1981) Validation and statistical analysis of a computer modeling method for quantitative analysis of radioligand binding data for mixtures of pharmacological receptor subtypes. Mol. Pharmacol. 21:5–16.
DeLean, A., Munson, P.J. and Rodbard, D. (1978) Simultaneous analysis of families of sigmoidal curves: Application to bioassay, radioligand assay and physiological dose-response curves. Am. J. Physiol. 235:E97–E102.
DeLean, A., Stadel, J.M. and Lefkowitz, R.J. (1980) A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled β-adrenergic receptor. J. Biol. Chem. 255:7108–7117.
Janin, J. (1973) The study of allosteric proteins. Prog. Biophys. Mol. Biol. 27:77–119.
Klotz, I.M. (1946) The application of the law of mass action to binding by proteins. Interactions with calcium. J. Am. Chem. Soc. 9:109–117.
Klotz, I.M. and Hunston, D.L. (1975) Protein interactions with small molecules: Relationships between stoichimetric binding constants, site binding constants, and empirical binding parameters. J. Biol. Chem. 250:3001–3009.
Koshland, D.E., Nemethy, G. and Filmer, D. (1966) Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochem. 5:365–385.
Molinoff, P.B., Wolfe, B.B. and Weiland, G.A. (1981) Quantitative analysis of drug-receptor interactions II. Determination of the properties of receptor subtypes. Life Sci. 29:427–443.
Munson, P.J. (1983) LIGAND: A computerized analysis of ligand binding data. Methods in Enzymology 92:543–546.
Newsholme, E.A. and C. Start (1973) Regulation in Metabolism, (ed.), ch. 2. New York: John Wiley and Sons.
Steinhardt, J. and Reynolds, J.A. (1969) Multiple Equilibria in Proteins, (ed.), ch. 2, pp. 10–33. New York: Academic Press.
Teipel, J. and Koshland, D.E. (1969) The significance of intermediary plateau regions in enzyme saturation curves. Biochem. 8:4656–4663.
Wregett, K.A. and DeLean, A. (1984) The ternary complex model. Its properties and application to ligand interactions with the D2-dopamine receptor of the anterior pituitary gland. Mol. Pharmacol. 26:214–227.
Cited
Adair, G.S. (1925) The hemoglobin system. VI. The oxygen dissociation curve of hemoglobin. J. Biol Chem. 63:529–545.
Barnett, D.B., Rugg, E.L. and Nahorski, S.R. (1978) Direct evidence of two types of β-adrenoceptor binding sites in lung tissue. Nature 273:166–168.
Birdsall, N.J.M., Hulme, E.C. and Burgen, A.S.V. (1980). The character of the muscarinic receptors in different regions of the rat brain. Proc. Roy. Soc. Lond. B. 207:1–12.
Burgisser, E., DeLean, A. and Lefkowitz, R.J. (1982) Reciprocal modulation of agonistand antagonist binding to muscarinic cholinergic receptors by guanine nucleotide. Proc. Natl. Acad. Sci. USA 79:1732–1736.
DeHaen, C. (1976) The non-stoichiometric floating receptor model for hormone sensitive adenylyl cyclase. J. Theoret. Biol. 58:383–400.
Feldman, H.A. (1972) Mathematical theory of complex ligand-binding systems at equilibrium: Some methods for parameter fitting. Anal. Biochem. 48:317–338.
Hoffman, B.B., DeLean, A., Wood, C.L., Schocken, D.D. and Lefkowitz, R.J. (1979) Alphaadrenergic receptor subtypes: Quantitative assessment by ligand binding. Life Sci. 24:1739–1746.
Hoffman, B.B. and Lefkowitz, R.J. (1980) An assay for alpha-adrenergic receptor subtypes using [3H]-dihydroergocryptine. Biochem. Pharmacol. 29:452–454.
Jacobs, S. and Cuatrecasas, P. (1976) The mobile receptor hypothesis and “cooperativity” of hormone binding. Application to insulin. Biochim. Biophys. Acta 433:482–495.
Katz, B. and Thesleff, S. (1957) A study of the “desensitization” produced by acetylcholine at the motor end plate. J. Physiol. 138:63–80.
Kent, R.S., DeLean, A. and Lefkowitz, R.J. (1980) A quantitative analysis of beta-adrenergic receptor interactions: Resolution of high and low affinity states of the receptor by computer modeling of ligand binding data. Mol. Pharmacol. 17:14–23.
Kilpatrick, B.V. and Caron, M.G. (1983) Agonist binding promotes a guanine nucleotide reversible increase in the apparent size of the bovine anterior pituitary dopamine receptors. J. Biol. Chem. 258:13528–13534.
Klotz, I.M. (1983) Ligand-receptor interactions: What we can and cannot learn from binding measurements. Trends in Pharmacol. Sci. 4:253–255.
Klotz, I.M. and Hunston, D.L. (1984) Mathematical models for ligand-receptor binding. Real sites, ghost sites. J. Biol. Chem. 259:10060–10062.
Lavin, T.N., Hoffman, B.B. and Lefkowitz, R.J. (1981) Determination of subtype selectivity of alpha-adrenergic ligands. Comparison of selective and non-selective radioligands. Mol. Pharmacol. 20:28–34.
Limbird, L.E., Gill, D.M. and Lefkowitz, R.J. (1980) Agonist-promoted coupling of the β-adrenergic receptor with the guanine nucleotide regulatory protein of the adenylate cyclase system. Proc. Natl. Acad. Sci. USA 77:775–779.
Michel, T.M., Hoffman, B.B., Lefkowitz, R.J. and Caron, M.G. (1981) Different sedimentation properties of agonist- and antagonist-labeled platelet alpha2-adrenergic receptors. Biochem. Biophys. Res. Commun. 100:1131–1134.
Minneman, K.P., Hegstrand, L.R. and Molinoff, P.B. (1979) Simultaneous determination of beta1 and beta2-adrenergic receptors in tissues containing both subtypes. Mol. Pharmacol. 16:34–46.
Munson, P.J. and Rodbard, D. (1980) LIGAND: A versatile computerized approach for characterization of ligand-binding systems. Anal. Biochem. 107:220–239.
Rugg, E.L., Barnett, D.L. and Nahorski, S.R. (1978) Coexistence of beta1 and beta2 adrenoceptors in mammalian lung: evidence from direct binding studies. Mol. Pharm. 14:996–1005.
Smith, S.K. and Limbird, L.E. (1981) Solubilization of human plateletα -adrenergic receptors: Evidence that agonist occupancy of the receptor stabilizes receptor-effector interactions. Proc. Natl. Acad. Sci. USA 78:4026–4030.
Weiland, G.A., Minneman, K.P. and Molinoff, P.B. (1979) Fundamental difference between the molecular interactions of agonists and antagonists with the β-adrenergic receptor. Nature 281:114–117.
Williams, L.T. and Lefkowitz, R.J. (1977) Slowly reversible binding of catecholamine to a nucleotide-sensitive state of the β-adrenergic receptor. J. Biol. Chem. 252:7207–7213.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 1986 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Limbird, L.E. (1986). Complex Binding Phenomena. In: Cell Surface Receptors: A Short Course on Theory and Methods. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1882-9_4
Download citation
DOI: https://doi.org/10.1007/978-1-4757-1882-9_4
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-1884-3
Online ISBN: 978-1-4757-1882-9
eBook Packages: Springer Book Archive