Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors.
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.
Mailliet
François
F
UMR INRA-CNRS-Université de Tours 6073, Physiologie de la Reproduction et des Comportements, Nouzilly 37380, France.
Audinot
Valérie
V
Malpaux
Benoit
B
Bonnaud
Anne
A
Delagrange
Philippe
P
Migaud
Martine
M
Barrett
Perry
P
Viaud-Massuard
Marie-Claude
MC
Lesieur
Daniel
D
Lefoulon
François
F
Renard
Pierre
P
Boutin
Jean A
JA
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
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)