5-MCA-NAT does not act through NQO2 to reduce intraocular pressure in New-Zealand white rabbit.
Solid data support the idea that the MT(3) melatonin binding site is an enzyme, quinone reductase 2 (NQO2), rather than a membrane melatonin receptor. However, the melatonin analogue, 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT), reduces intraocular pressure (IOP) via MT(3) melatonin receptors. Therefore, the aim of this work was to test whether the melatonin binding site, MT(3), is indeed the enzyme NQO2 in New Zealand rabbit eyes. To investigate this, the action of several substrates and inhibitors for NQO2 was compared to 5-MCA-NAT in their ability to modify IOP. Also, the effect of 5-MCA-NAT on IOP produced after NQO2 silencing by means of a siRNA was determinated. Altogether, the results led us to conclude that the in vivo effect of the MT(3) ligand 5-MCA-NAT on IOP is not mediated by the enzyme NQO2, suggesting the existence of another melatonin receptor.
Alarma-Estrany
Pilar
P
Crooke
Almudena
A
Pintor
Jesús
J
Departamento Bioquímica, E.U. Óptica, Universidad Complutense de Madrid, C/Arcos de Jalón s/n, Madrid, Spain.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002738:Chloroquine / Q000494:pharmacology; D002924:Ciliary Body / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000187:drug effects*; D008969:Molecular Sequence Data; D011808:Quinone Reductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D011817:Rabbits; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077185:Resveratrol; D016415:Sequence Alignment; D013267:Stilbenes / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology*; D024483:Vitamin K 3 / Q000494:pharmacology
C413586:5-methoxycarbonylamino-N-acetyltryptamine; D034741:RNA, Small Interfering; D044094:Receptors, Melatonin; D013267:Stilbenes; D014363:Tryptamines; D024483:Vitamin K 3; D002738:Chloroquine; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases; D000077185:Resveratrol