title: High-throughput screening assay for new ligands at human melatonin receptors.
abstract: OBJECTIVE
  Melatonin (MT) is a neurohormone produced and secreted primarily by the pineal gland in a circadian manner, and mainly acts through 2 receptor subtypes: MT1 and MT2 in humans. The diversity in their tissue distribution is in favor of different functions for each receptor subtype. Selective modulators are therefore required to determine the physiological roles of these melatonin receptor subtypes and their implications in pathological processes.
  
  
  METHODS
  A homogenous MT1/MT2 receptor binding assay was established for high-throughput screening of new ligands at the hMT1 and/or hMT2 receptors. The functional properties (agonists or antagonists) were assessed by a conventional guanosine-5'[gamma-(35)S] triphosphate (GTP-gammaS) assay.
  
  
  RESULTS
  Three hMT1 receptor-selective small molecule antagonists and 1 hMT2 receptor-selective small molecule antagonist with novel structural features were identified following a high-throughput screening campaign of 48,240 synthetic and natural compounds.
  
  
  CONCLUSIONS
  The findings may assist in the expansion of chemical probes to these 2 receptor subtypes.
authors.affiliation: The National Center for Drug Screening and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Yan
authors.forename: Hao-ran
authors.initials: HR
authors.lastname: Su
authors.forename: Jean A
authors.initials: JA
authors.lastname: Boutin
authors.forename: M Pierre
authors.initials: MP
authors.lastname: Renard
authors.forename: Ming-wei
authors.initials: MW
authors.lastname: Wang
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D008550:Melatonin / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D011869:Radioligand Assay / Q000379:methods*; D044122:Receptor, Melatonin, MT1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D008024:Ligands; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin