Receptor interactions, determination

Fig. 1.5. Activation of the native receptor by thehormone. The hormone-receptor interaction determines a very strong bond that attracts distant amino acid residues, which alters the three-dimensional structure of the receptor. As a consequence, the receptor loses its affinity for the proteins that were originally close but that no longer find their zones of contact with the receptor. Simultaneously, the receptor reorganizes other hormone-dependent zones it acquires dimerization capacity and exhibits a capacity to bind to DNA and to transcription factors. The interaction with antiestrogens also produces a conformational change, which can give rise or not to the formation of dimers, in any case with a different conformation...

The Kd of the agonist-receptor interaction determines what fraction (B/Bmax) of total receptors will be occupied at a given free concentration (C) of agonist regardless of the receptor concentration ... 

A. P. Mazurek, H. Weinstein, R. Osman, S. Topiol, and B. J. Ebersole, Int. J. Quantum Chem., Quantum Biol. Symp., 11, 183 (1984). Theoretical and Experimental Studies of Drug-Receptor Interactions Determinants for Recognition of 5-Hydroxytryptamine Analogs. 

Direct quantitation of receptor concentrations and dmg—receptor interactions is possible by a variety of techniques, including fluorescence, nmr, and radioligand binding. The last is particularly versatile and has been appHed both to sophisticated receptor quantitation and to dmg screening and discovery protocols (50,51). The use of high specific activity, frequendy pH]- or p lj-labeled, dmgs bound to cmde or purified cellular materials, to whole cells, or to tissue shces, permits the determination not only of dmg—receptor saturation curves, but also of the receptor number, dmg affinity, and association and dissociation kinetics either direcdy or by competition. Complete theoretical and experimental details are available (50,51). 

The Pharmacological Phenotype of Certain Family B Receptors Is Determined by Interaction with RAMPs... 

A lack of agreement between the Kj estimated in equilibrium experiments and that determined in kinetic experiments (k i/ki = Kd) suggests a more complex ligand-receptor interaction. 

Wieland GA, Molinoff PB. 1981. Quantitative analysis of drug-receptor interactions I. Determination of kinetic and equilibrium properties. Life Sci 29 313. 

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