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

Authors: Alarma-Estrany, Pilar; Crooke, Almudena; Pintor, Jesús

Source: Journal of Pineal Research, Volume 47, Number 2, September 2009 , pp. 201-209(9)

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Abstract:

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.

Keywords: 5-methoxycarbonylamino-N-acetyltryptamine; intraocular pressure; melatonin; MT3 melatonin receptor; quinone reductase 2

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1600-079X.2009.00702.x

Publication date: 2009-09-01