5-MCA-NAT does not act through NQO2 to reduce intraocular pressure in New-Zealand white rabbit

Solid data support the idea that the MT3 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 MT3 melatonin receptors. Therefore, the aim of this work was to test whether the melatonin binding site, MT3, 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 MT3 ligand 5-MCA-NAT on IOP is not mediated by the enzyme NQO2, suggesting the existence of another melatonin receptor.