By Arnost Kleinzeller and B. Richard Martin (Eds.)
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3. ASSUMPTIONS AND LIMITATIONS OF THE SEQUENTIAL MODELS: THE RAPIDEQUILIBRIUM The sequential models depart from the one-step models in two important respects. 1. The ligand has changed its role. In the one-step models the role of the ligand is to initiate a signal and a response. The nature of the signal vis-h-vis the response in molecular terms remains obscure. In the sequential models, the role of the ligand is to alter the affinity between R and E. This in itself gives the concept of efficacy a sound physical basis: each ligand would have its own potential to alter the affinity between R and E.
What constitutes a quantitative solution to this formal statement depends on our ability to express the magnitude of the response in terms of the components which cause its creation. In this case the components are L,, the total ligand concentration, R,, the total receptor concentration, and the rate constants, 1 , 2, and a . For example, when equilibrium between L and R is achieved and L, = Lfree the following expression is obtained ( t is time): response = dRTtl(211 + L) (2) Three parameters are sufficient to characterize the behavior of this system: the equilibrium constant 2/1, the total receptor concentration R,, and the proportionality constant a.
1980). A probe for the organisation of the P-adrenergic receptor-regulated adenylate cyclase system in turkey erythrocyte plasma membranes by the use of a complementation assay. FEBS Lett. 122, 179-183. , and Schramm, M. (1976). Coupling of catecholamine receptor from one cell with adenylate cyclase from another cell by cell fusion. Proc. Nail. Acad. Sci. A. 73, 4410-4414. Pfeufer. , and Helmreich, E. J . M. (1975). Activation of pigeon erythrocyte plasma membrane adenylate cyclase by guanyl nucleotide analogues and separation of a nucleotide binding protein.
Membrane Receptors by Arnost Kleinzeller and B. Richard Martin (Eds.)