Theoretical implications of receptor coupling to multiple G proteins based on analysis of a three-state model.

Publisher Summary This chapter provides a mechanistic basis for explaining variable agonist pharmacology in so-called promiscuous receptor systems. It describes the way by which a single receptor type, when coupled to more than one signaling pathway, can exhibit different potency orders, different efficacy orders, and variable propensity to inverse agonism. It predicts that such variable pharmacological behavior can arise from the use of different response measurements and under conditions of variable receptor: G protein stoichiometry. It is important to emphasize that such pharmacological observations would, according to earlier theoretical models, be attributed to differences in receptor types. Such differences may arise in a number of ways: the use of different recombinant receptor expression systems, the use of different primary cell lines, the use of G protein toxins, and receptor/G protein compartmentalization.