title: Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors.
abstract: The variations of the pharmacological properties of melatonin receptors between different mammalian species in transfected cell lines have been poorly investigated. In the present study, melatonin analogues have been used to characterize the pharmacology of the recombinant ovine melatonin receptor (oMT1) expressed in CHO cell lines and the native oMT1 from the pars tuberalis (PT). Studies with selective ligands on native and transfected oMT1 showed similar properties for binding affinities [r2(PT/CHO) = 0.85]. The affinities and the functional activities of these ligands were compared with the human receptors (hMT1 or hMT2) expressed in CHO cells as well. The oMT1 and hMT1 receptors had similar pharmacological profiles (r2=0.82). Nevertheless, some of the selective compounds at the human receptor presented a reduced affinity at the ovine receptor. Furthermore, some compounds showed marked different functional activities at oMT1 vs. hMT1 receptors. Our findings demonstrated differences in the pharmacological properties of melatonin receptors in ovine and human species.
authors.affiliation: UMR INRA-CNRS-Université de Tours 6073, Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France.
authors.forename: François
authors.initials: F
authors.lastname: Mailliet
authors.forename: Valérie
authors.initials: V
authors.lastname: Audinot
authors.forename: Benoit
authors.initials: B
authors.lastname: Malpaux
authors.forename: Anne
authors.initials: A
authors.lastname: Bonnaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.forename: Martine
authors.initials: M
authors.lastname: Migaud
authors.forename: Perry
authors.initials: P
authors.lastname: Barrett
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Viaud-Massuard
authors.forename: Daniel
authors.initials: D
authors.lastname: Lesieur
authors.forename: François
authors.initials: F
authors.lastname: Lefoulon
authors.forename: Pierre
authors.initials: P
authors.lastname: Renard
authors.forename: Jean A
authors.initials: JA
authors.lastname: Boutin
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D011869:Radioligand Assay; D044122:Receptor, Melatonin, MT1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D044094:Receptors, Melatonin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D034561:Sheep, Domestic; D013045:Species Specificity; D013462:Sulfur Radioisotopes; D014162:Transfection
chemical_list: D007457:Iodine Radioisotopes; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D044094:Receptors, Melatonin; D011994:Recombinant Proteins; D013462:Sulfur Radioisotopes; D016244:Guanosine 5'-O-(3-Thiotriphosphate)