PT - JOURNAL ARTICLE AU - Andrejs M. Krumins AU - Roger Barber TI - The Stability of the Agonist β<sub>2</sub>-Adrenergic Receptor-G<sub>s</sub> Complex: Evidence for Agonist-Specific States AID - 10.1124/mol.52.1.144 DP - 1997 Jul 01 TA - Molecular Pharmacology PG - 144--154 VI - 52 IP - 1 4099 - http://molpharm.aspetjournals.org/content/52/1/144.short 4100 - http://molpharm.aspetjournals.org/content/52/1/144.full SO - Mol Pharmacol1997 Jul 01; 52 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.