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Article

International Union of Basic and Clinical Pharmacology. LXVII. Recommendations for the Recognition and Nomenclature of G Protein-Coupled Receptor Heteromultimers

Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut de Génomique Fonctionnelle, Institut National de la Santé et de la Recherche Médicale U661, Université de Montpellier 1 and 2, Montpellier, France (J.-P.K.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (R.N.); Unité de Recherche en Pharmacologie Moléculaire, Institut de Recherche en Immunologie et Cancérologie, Université de Montreal, Montreal, Quebec, Canada (M.B.); Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York (L.D.); Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York (M.F.); Center for Molecular Recognition and Departments of Psychiatry and Pharmacology, Columbia University College of Physicians and Surgeons, New York, New York (J.A.J.); Department of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany (M.J.L.); Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland (G.M.); Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio (K.P.); Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium (M.P.); and Institute of Research Servier, Suresnes, France (M.S.)

Abstract

I. Introduction

II. The Class C G Protein-Coupled Receptors

III. The Class A G Protein-Coupled Receptors

A. Rhodopsin

B. The Melatonin Receptor

C. The Glycoprotein Hormone Receptors

D. The Opioid Receptors

E. The CCR2 and CCR5 Receptors

F. The AT1 and Mas Receptors

G. The alpha1B and alpha1D Adrenoceptors

H. The beta1 and beta2 Adrenoceptors

IV. On the Nomenclature and Recognition of Multimeric G Protein-Coupled Receptors

G protein-coupled receptors (GPCRs) have long been considered to be monomeric membrane proteins. Although numerous recent studies have indicated that GPCRs can form multimeric complexes, the functional and pharmacological consequences of this phenomenon have remained elusive. With the discovery that the functional GABA_B receptor is an obligate heterodimer and with the use of energy transfer technologies, it is now accepted that GPCRs can form heteromultimers. In some cases, specific properties of such heteromers not shared by their respective homomers have been reported. Although in most cases these properties have only been observed in heterologous expression systems, there are a few reports describing data consistent with such heteromultimeric GPCR complexes also existing in native tissues. The present article illustrates well-documented examples of such native multimeric complexes, lists a number of recommendations for recognition and acceptance of such multimeric receptors, and gives recommendations for their nomenclature.

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