title: Molecular and cellular pharmacological properties of 5-methoxycarbonylamino-N-acetyltryptamine (MCA-NAT): a nonspecific MT3 ligand.
abstract: 5-Methoxycarbonylamino-N-acetyltryptamine (MCA-NAT) has been initially described as a ligand at non MT(1), non MT(2) melatonin binding site (MT3) selective versus MT(1) and MT(2), two membrane melatonin receptors. MCA-NAT activity has been reported by others in different models, in vivo, particularly in the intra-ocular pressure (IOP) models in rabbits and monkeys. Its activity was systematically linked to either MT3 or to a new, yet unknown, melatonin receptor. In this article, the melatonin receptor pharmacology of MCA-NAT is described. MCA-NAT has micromolar range affinities at the melatonin receptors MT(1) and MT(2), while in functional studies, MCA-NAT proved to be a powerful MT(1)/MT(2) partial agonist in the sub-micromolar range. These data strongly suggest that MCA-NAT actions might be mediated by these receptors in vivo. Finally, as described by others, we show that MCA-NAT is unable to elicit any type of receptor-like functional responses from Chinese hamster ovary cells over-expressing quinone reductase 2, the MT3.
authors.affiliation: Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, Croissy-sur-Seine, France.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Vincent
authors.affiliation: Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, Croissy-sur-Seine, France.
authors.forename: William
authors.initials: W
authors.lastname: Cohen
authors.affiliation: Département des Sciences Expérimentales, Institut de Recherches Servier, Suresnes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.affiliation: Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, Croissy-sur-Seine, France.
authors.forename: Jean A
authors.initials: JA
authors.lastname: Boutin
authors.affiliation: Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, Croissy-sur-Seine, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Nosjean
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D002942:Circular Dichroism; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D000882:Haplorhini; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D000090023:Metallothionein 3; D051379:Mice; D011817:Rabbits; D051381:Rats; D044094:Receptors, Melatonin / Q000378:metabolism*; D014363:Tryptamines / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: C413586:5-methoxycarbonylamino-N-acetyltryptamine; D007295:Inositol Phosphates; D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D044094:Receptors, Melatonin; D014363:Tryptamines; D005576:Colforsin; D000242:Cyclic AMP