Abstract

A mathematical model is presented that simulates the steady state kinetics of agonists interacting with a promiscuous receptor. The model system consists of a single receptor that forms a ternary complex with either of two transducer proteins (G proteins). At a given agonist concentration, the concentrations of the two ternary complexes are determined by the relative quantities of the two G proteins and the ratio of the dissociation constants for the two ternary complexes. Accordingly, the potency of an agonist is dependent upon the relative quantities of the G proteins. If receptors are truly promiscuous and if the distribution of G proteins varies with tissue type, then the agonist potency ratio would be tissue dependent as well as receptor dependent. Experimental data from literature studies are reviewed in the context of the promiscuous receptor model, and implications of the model regarding pharmacologic classification of receptors are discussed.