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.