Abstract
Detailed structure-activity relationships of many drugs and hormones indicate that ligand-receptor binding involves the interaction of several functional regions on the ligand with complementary receptor "subsites." However most hormone receptor binding models have been based on a simple bimolecular reaction obeying the mass action law. We present a quantitative reinterpretation in pharmacological terms of the theory of flexible polyvalent ligand binding. The model explains: 1) the occurrence of complex binding isotherms showing both apparent heterogeneous and cooperative binding sites; 2) bell-shaped dose response curves; 3) the properties of full and partial agonists; 4) how a given antagonist can be either "competitive" or "noncompetitive" depending on concentration used. The classical simple bimolecular interaction between drug and receptor is a limiting case of the model, when steric hindrance completely prevents multiple receptor occupancy, or when the ligand and the receptor interact in an all-or-none mode.
ACKNOWLEDGMENTS Charles De Lisi kindly reviewed the manuscript and provided many helpful suggestions. The numerical analysis was based in part on the methods of Feldman (39).
- Copyright © 1979 by Academic Press, Inc.
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