title: New radioligands for describing the molecular pharmacology of MT1 and MT2 melatonin receptors.
abstract: Melatonin receptors have been studied for several decades. The low expression of the receptors in tissues led the scientific community to find a substitute for the natural hormone melatonin, the agonist 2-[125I]-iodomelatonin. Using the agonist, several hundreds of studies were conducted, including the discovery of agonists and antagonists for the receptors and minute details about their molecular behavior. Recently, we attempted to expand the panel of radioligands available for studying the melatonin receptors by using the newly discovered compounds SD6, DIV880, and S70254. These compounds were characterized for their affinities to the hMT1 and hMT2 recombinant receptors and their functionality in the classical GTPS system. SD6 is a full agonist, equilibrated between the receptor isoforms, whereas S70254 and DIV880 are only partial MT2 agonists, with Ki in the low nanomolar range while they have no affinity to MT1 receptors. These new tools will hopefully allow for additions to the current body of information on the native localization of the receptor isoforms in tissues.
authors.affiliation: BPMC, Institut de Recherches SERVIER, 125 chemin de Ronde, Croissy-sur-Seine 78290, France. jean.boutin@fr.netgrs.com.
authors.forename: Céline
authors.initials: C
authors.lastname: Legros
authors.forename: Ulrich
authors.initials: U
authors.lastname: Matthey
authors.forename: Teresa
authors.initials: T
authors.lastname: Grelak
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pedragona-Moreau
authors.forename: Werner
authors.initials: W
authors.lastname: Hassler
authors.forename: Saïd
authors.initials: S
authors.lastname: Yous
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Thomas
authors.forename: Franck
authors.initials: F
authors.lastname: Suzenet
authors.forename: Benoît
authors.initials: B
authors.lastname: Folleas
authors.forename: François
authors.initials: F
authors.lastname: Lefoulon
authors.forename: Pascal
authors.initials: P
authors.lastname: Berthelot
authors.forename: Daniel-Henri
authors.initials: DH
authors.lastname: Caignard
authors.forename: Gérald
authors.initials: G
authors.lastname: Guillaumet
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Brayer
authors.forename: Olivier
authors.initials: O
authors.lastname: Nosjean
authors.forename: Jean A
authors.initials: JA
authors.lastname: Boutin
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008550:Melatonin / Q000031:analogs & derivatives / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000378:metabolism*; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012044:Regression Analysis
chemical_list: D008024:Ligands; D019275:Radiopharmaceuticals; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D011994:Recombinant Proteins; C044556:2-iodomelatonin; D008550:Melatonin