Characterisation of human melatonin mt(1) and MT2 receptors by CRE-luciferase reporter assay

A cyclic AMP response element (CRE)-luciferase reporter gene assay was used to characterise the functional responses of human melatonin mt(1) and huma n melatonin MT2 receptors, stably expressed in the human embryonic kidney c ell line HEK293, to a series of six naphthalenic analogues of melatonin. By comparison to the observed melatonin-mediated inhibition of stimulated luc iferase levels the naphthalenic series was identified as comprising agonist s, partial agonists and one antagonist of melatonin mt(1) and melatonin MT2 receptor function. Three of the agonist/partial agonist members of this se ries were also identified as displaying a functional selectivity for the me latonin MT2 receptor. Competitive displacement of 2-[I-125]iodomelatonin bi nding to the ovine pars tuberalis melatonin ML1 receptor demonstrated a clo se correlation to the observed functional luciferase responses of the human melatonin mt(1) receptor. We conclude that the CRE-luciferase reporter gen e assay provides an effective functional screening method for the pharmacol ogical characterisation of human melatonin receptor subtypes. (C) 2000 Else vier Science B.V. All rights reserved.