Inverse agonism: the classic concept of GPCRs revisited [Review]
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- Sato Junichiro
- Department of Endocrinology and Nephrology, The University of Tokyo School of Medicine, Tokyo 113-8655, Japan
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- Makita Noriko
- Department of Endocrinology and Nephrology, The University of Tokyo School of Medicine, Tokyo 113-8655, Japan
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- Iiri Taroh
- Department of Endocrinology and Nephrology, The University of Tokyo School of Medicine, Tokyo 113-8655, Japan Department of Pharmacology, St. Marianna University, Kawasaki 216-8511, Japan
抄録
In the classical two-state model, G protein-coupled receptors (GPCRs) are considered to exist in equilibrium between an active and an inactive conformation. Thus, even at the resting state, some subpopulation of GPCRs is in the active state, which underlies the basal activity of the GPCRs. In this review, we discuss inverse agonists, which are defined as GPCR ligands that shift the equilibrium toward the inactive state and thereby suppress the basal activity. Theoretically, if constitutive activation plays an essential role in the pathogenesis of a disease, only inverse agonists, and not neutral antagonists, can reverse this pathophysiological activation. Although many pharmacological examples of inverse agonism have been identified, its clinical importance is still unclear and debated. Thus, even though inverse agonism of angiotensin receptor blockers (ARBs) has been discussed for more than 10 years, its clinical relevance remains to be completely clarified.
収録刊行物
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- Endocrine Journal
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Endocrine Journal 63 (6), 507-514, 2016
一般社団法人 日本内分泌学会
