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Description of the constitutive activity of cloned human melatonin receptors hMT 1 and hMT 2 and discovery of inverse agonists
Author(s) -
Devavry Séverine,
Legros Céline,
Brasseur Chantal,
Delagrange Philippe,
Spadoni Gilberto,
Cohen William,
Malpaux Benoît,
Boutin Jean A.,
Nosjean Olivier
Publication year - 2012
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2011.00968.x
Subject(s) - melatonin , receptor , melatonin receptor , biology , g protein coupled receptor , microbiology and biotechnology , chinese hamster ovary cell , inverse agonist , signal transduction , intracellular , agonist , endocrinology , biochemistry
Abstract: Melatonin receptors have been described to activate different G protein–dependent signaling pathways, both in laboratory, heterologous, cellular models and in physiological conditions. Furthermore, the constitutive activity of G protein–coupled receptors has been shown to be key in physiological and pathological conditions. In the case of melatonin receptors, information is rather scare and concerns only MT1 receptors. In the present report, we show that the G protein–coupled melatonin receptors do have a constitutive, nonmelatonin‐induced signaling activity using two cellular models of different origins, the Chinese hamster ovary cell line and Neuro2A, a neuroblastoma cell line. Furthermore, we show that this constitutive activity involves mainly Gi proteins, which is consistent with the common knowledge on the melatonin receptors. Importantly, we also describe, for the first time, inverse agonist properties for melatonin ligands. Although it is clear than more in‐depth, biochemistry‐based studies will be required to better understand by which pathway(s) the constitutively active melatonin receptors transfer melatonin information into intracellular biochemical events; our data open interesting perspectives for understanding the importance of the constitutive activity of melatonin receptors in physiological conditions.