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2-Adrenergic
Receptor-Gs Complex: Evidence for Agonist-Specific States
Department of Integrative Biology, Pharmacology, and
Physiology, University of Texas-Houston Medical School, Houston,
Texas 77225-0334
A restricted version of the ternary complex model for receptor-G
protein complex formation has recently been proposed. Known as the
two-state model, this model proposes that in the context of agonist and
G protein interactions, only two thermodynamic states exist for the
receptor: active (R*) and inactive (R). One form of this model suggests
that only the R* state of the receptor is capable of interacting with
and subsequently activating G proteins. We directly tested the kinetic
aspects of a strict two-state receptor model in a cell line containing
the native 
2-adrenergic receptor that is capable of
inducing Gs expression. We examined adenylyl cyclase
activity in the presence of limiting GTP levels and concluded that
there exists a different rate of heterotrimer dissociation (i.e., HR*G
yields HR* + G*) for different 2-agonists. This finding is inconsistent with a strict two-state model in which R* is a characteristic of the receptor that is independent of the identity of
the agonist. It implies that agonist activation of adenylyl cyclase is
more complicated than a simple two-state model.
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