On the Contributions of RXComplex and Agonist-Receptor Complex to Formation of the Ternary Complex: Results of a New Method of Analysis

More than 2 decades ago it was demonstrated that responses of some well-studied biochemical systems were not proportional to occupation of receptors by hormones specific for the receptors, even when the receptors were considered to be very closely coupled to the response. A plausible hypothesis devised to account for some of those results involved the formation of a ternary complex consisting of receptorRhormone (or transmitter) ligandLand so-called regulatory or transducer proteinX. st successful experimental-theoretical study of such a system was that of DeLeanet al.(1980) who showed that the adenylate cyclase-linked β-adrenergic system of frog erythrocyte membranes conformed closely to the theoretical model of Jacobs & Cuatrecasas (1976). Not only did conformity to the theory require the formation of ternary complexX̄but also of significant quantities of binary complexX̄X̄as well. & Leff (1983) were the first to adapt the ternary complex hypothesis to describe experiments of the types commonly carried out by pharmacologists. It was later utilized for this purpose by others such as Mackay (1987, 1988), Morganet al.(1988), Jenkinson (1989) and Leff & Harper (1989). Although all of these writers gave due attention to the ternary complex in their formulations, they omitted from their calculations theX̄complex to whose significance DeLeanet al.had drawn attention. following treatment we have reconsidered the role of the binaryX̄complex from new points of view and have shown thatRX̄complex contributed to formation of the ternary complex in the experiments of DeLeanet al.but that agonist-receptor complex did not do so. These results contradict the suggestion of DeLeanet al.concerning the “simplest” mechanistic explanation of their observations.