The melatonin analog 5-MCA-NAT increases endogenous dopamine levels by binding NRH:quinone reductase enzyme in the developing chick retina.

Autor: Sampaio Lde F; Lab. de Bioquímica do Desenvolvimento do Sistema Nervoso, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa No. 1, CEP: 66075-110 Belém, PA, Brazil. Electronic address: lsampaio@ufpa.br., Mesquita FP; Lab. de Bioquímica do Desenvolvimento do Sistema Nervoso, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa No. 1, CEP: 66075-110 Belém, PA, Brazil., de Sousa PR; Lab. de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Rua Augusto Corrêa No. 1, CEP: 66075-110 Belém, PA, Brazil., Silva JL; Lab. de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Rua Augusto Corrêa No. 1, CEP: 66075-110 Belém, PA, Brazil., Alves CN; Lab. de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Rua Augusto Corrêa No. 1, CEP: 66075-110 Belém, PA, Brazil.
Jazyk: angličtina
Zdroj: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience [Int J Dev Neurosci] 2014 Nov; Vol. 38, pp. 119-26. Date of Electronic Publication: 2014 Sep 10.
DOI: 10.1016/j.ijdevneu.2014.09.001
Abstrakt: NRH:quinone reductase (QR2) is present in the retinas of embryonic and post-hatched (PH) chicks. 5-Methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) is a QR2 ligand that increases cAMP levels in developing retinas, but it does not affect cAMP levels in CHO-QR2 cells. The dopamine quinone reductase activity of QR2 retrieves dopamine, which increases cAMP levels in developing retinas. The objective of the present study was to investigate whether 5-MCA-NAT increases endogenous dopamine levels in retinas from chick embryos and post-hatched chicks. Endogenous dopamine was measured by enzyme-linked immunosorbent assay (ELISA). 5-MCA-NAT increased retinal endogenous dopamine levels at all developmental stages studied and in PH chicks (-logEC50=11.62±0.34 M). This effect was inhibited by non-selective antagonists of receptors and melatonin binding sites N-acetyl-2-benzyltryptamine (luzindole, 5 μM), but it was not inhibited by the Mel1b melatonin receptor antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT, 10 nM). The QR2 cosubstrate, N-methyl-dihydronicotinamide (NMH) (-logEC50=6.74±0.26 M), increased endogenous dopamine levels in controls and in retinas stimulated with 5-MCA-NAT (3 nM). The QR2 inhibitor benzo[e]pyrene inhibited endogenous dopamine levels in both control (-logIC50=7.4±0.28 M) and NMH-stimulated (at 100 nM and 1 μM benzo[e]pyrene concentrations) retinas. Theoretical studies using Molegro Virtual Docking software corroborated these experimental results. We conclude that 5-MCA-NAT increases the level of endogenous dopamine via QR2. We suggest that this enzyme triggers double reduction of the dopamine quinone, recovering dopamine in retinal development.
(Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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