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Melatonin MT 1 and MT 2 receptors display different molecular pharmacologies only in the G ‐protein coupled state
Author(s) -
Legros Céline,
Devavry Séverine,
Caignard Sarah,
Tessier Clémence,
Delagrange Philippe,
Ouvry Christine,
Boutin Jean A,
Nosjean Olivier
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12457
Subject(s) - melatonin , receptor , melatonin receptor , biology , g protein , radioligand , microbiology and biotechnology , biochemistry , g protein coupled receptor , biophysics , chemistry , endocrinology
Background and Purpose Melatonin receptors have been extensively characterized regarding their affinity and pharmacology, mostly using 2‐[ 125 I ]‐melatonin as a radioligand. Although [ 3 H ]‐melatonin has the advantage of corresponding to the endogenous ligand of the receptor, its binding has not been well described. Experimental Approach We characterized [ 3 H ]‐melatonin binding to the hMT 1 and hMT 2 receptors expressed in a range of cell lines and obtained new insights into the molecular pharmacology of melatonin receptors. Key Results The binding of [ 3 H ]‐melatonin to the hMT 1 and hMT 2 receptors displayed two sites on the saturation curves. These two binding sites were observed on cell membranes expressing recombinant receptors from various species as well as on whole cells. Furthermore, our GTP γ S / NaCl results suggest that these sites on the saturation curves correspond to the G ‐protein coupled and uncoupled states of the receptors, whose pharmacology was extensively characterized. Conclusions and Implications hMT 1 and hMT 2 receptors spontaneously exist in two states when expressed in cell lines; these states can be probed by [ 3 H ]‐melatonin binding. Overall, our results suggest that physiological regulation of the melatonin receptors may result from complex and subtle mechanisms, a small difference in affinity between the active and inactive states of the receptor, and spontaneous coupling to G ‐proteins.