Abstract
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.
Footnotes
- Received December 26, 1996.
- Accepted April 4, 1997.
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Send reprint requests to: Roger Barber, Ph.D., The University of Texas-Houston Medical School, Department of Integrative Biology, Pharmacology, and Physiology, 6431 Fannin, P.O. Box 20708, Houston, TX 77225-0334. E-mail:rbarber{at}farmr1.med.uth.tmc.edu
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This work was supported by National Institutes of Health Grant RR07710.
- The American Society for Pharmacology and Experimental Therapeutics
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