Interconverting receptor model

Figure 6. Interconverting receptor model. In the presence of L, membrane R and G become associated to form the ternary complex LRG, which is sequentially interconverted into LR and LRX prior to internalization.

However, based on the concept that GPCRs are able to adopt a variety of conformations, an extended model can also be described, as shown in Figure 2. In this extended cubic ternary complex model of receptor activation and modulation, the receptor can interconvert between an active (R) and an inactive conformation (R), each with a different... 

The term state rather than condition is often used in this context. However, the latter seems preferable in an introductory account. This is because the del Castillo-Katz mechanism is often described as a two-state model of receptor action, meaning here that the occupied receptor exists in two distinct (albeit interconvertible) forms, AR and AR, whereas three conditions of the receptor (R, AR, and AR ) have to be identified when applying the law of mass action to the binding of the ligand, A. 

As mentioned earlier, current models of receptor function provide for receptor conformations that interconvert between inactive and active states. The agonist-directed trafficking of receptor stimulus hypothesis suggests that there are multiple active conformations of a receptor that differ in their capacity to couple/activate effector pathways. Such multistate models predict that, like agonist-stimulated responses, constitutive receptor activity and the relative efficacy of inverse agonists should also be response dependent (Fig. 6). 

The mechanism of action of agents such as DMCM as inverse agonists has been explained in terms of a two-state model for the benzodi-azepine-GABA receptor complex (162). The model proposes that the complex exists in equilibrium between interconvertable open and closed channel conformations. GABA and BZR agonists such as diazepam exhibit recip-... 

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