For years, the AT2R-selective ligand CGP42112 has been erroneously characterized as a partial agonist, partly due to its ability to also interact with the AT1R at high concentrations. As late as 2009, it was still being characterized as an antagonist as well. In this perspective/opinion piece, we try to resolve the ambiguity that surrounds the efficacy of this compound by extensively reviewing the literature, tracing its beginnings to 1989, showing that CGP42112 has never been convincingly shown to be a partial agonist or an antagonist at the AT2R. While CGP42112 is now routinely characterized as an AT2R agonist, regrettably, there is a paucity of studies that can validate its efficacy as a full agonist at the AT2R, leaving the door open for continuing speculation regarding the extent of its efficacy. Hopefully, the information presented in this perspective/opinion piece will firmly establish CGP42112 as a full agonist at the AT2R such that it can once again be used as a tool to study the AT2R.
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Evolving views on the first two ligands of the angiotensin II type 2 receptor. From putative antagonists to potential agonists?
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Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG, Groningen, the Netherlands. Electronic address:
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Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, U.S.A.
For years, the AT2R-selective ligand CGP42112 has been erroneously characterized as a partial agonist, partly due to its ability to also interact with the AT1R at high concentrations. As late as 2009, it was still being characterized as an antagonist as well. In this perspective/opinion piece, we try to resolve the ambiguity that surrounds the efficacy of this compound by extensively reviewing the literature, tracing its beginnings to 1989, showing that CGP42112 has never been convincingly shown to be a partial agonist or an antagonist at the AT2R.
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Am J Physiol Regul Integr Comp Physiol
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Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-1514, USA.
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Département de Physiologie et Pharmacologie Clinique, Centre National de la Recherche Scientifique, URA 1483, Faculté de Pharmacie, Lyon, France.
Angiotensin II recognizes two receptor subtypes, AT1 and AT2, both of them having been recently cloned. Although AT2 receptors represent 5-10% of angiotensin II receptors in the kidneys of adult rats, their function remains unknown. In the present work, we examined the possible contribution of AT2 receptors to the regulation of pressure-natriuresis in anesthetized rats infused either with the specific AT2 antagonist PD 123319, or with CGP 42112B, an AT2 ligand with agonistic properties.
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