THE CUBIC TERNARY COMPLEX RECEPTOR-OCCUPANCY MODEL .1. MODEL DESCRIPTION

In this paper we propose a new equilibrium model of the interactions b etween receptors, ligands, and G-proteins-the cubic ternary complex (C TC) model. The CTC model is a generalization of the extended ternary c omplex model of Samama et al. (1993). It incorporates all the features of that model but differs in that it also allows G-proteins to bind t o inactive receptors. The addition of this feature produces a complete equilibrium description of the three-way interactions between ligand, receptor, and G-proteins. We show that the standard equilibrium recep tor-occupancy models of pharmacology are equivalent to the hierarchica l log-linear models of statistics. Using this equivalence, we derive t he completeness of the CTC model from both a graphical and a statistic al perspective. In its simplest instance (one receptor, one G-protein, and one ligand) the CTC model consists of eight receptor species that can be graphically visualized as occupying the vertices of a cube. St atistically, the CTC model is a saturated three-factor log-linear mode l. Viewed statistically or graphically, other equilibrium binary and t ernary complex models are subsets of the CTC model. (C) 1996 Academic Press Limited