RT Journal Article
SR Electronic
T1 The Stability of the Agonist β<sub>2</sub>-Adrenergic Receptor-G<sub>s</sub> Complex: Evidence for Agonist-Specific States
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 144
OP 154
DO 10.1124/mol.52.1.144
VO 52
IS 1
A1 Andrejs M. Krumins
A1 Roger Barber
YR 1997
UL http://molpharm.aspetjournals.org/content/52/1/144.abstract
AB 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 β2-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 β2-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.