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Physiological concentrations of melatonin inhibit the nitridergic pathway in the Syrian hamster retina

Authors

  • Daniel A. Sáenz,

    1. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina, Buenos Aires, Argentina,
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  • Adrián G. Turjanski,

    1. Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, piso 3, Universidad de Buenos Aires, Conicet, Buenos Aires, Argentina
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  • Geraldine B. Sacca,

    1. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina, Buenos Aires, Argentina,
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  • Marcelo Marti,

    1. Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, piso 3, Universidad de Buenos Aires, Conicet, Buenos Aires, Argentina
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  • Fabio Doctorovich,

    1. Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, piso 3, Universidad de Buenos Aires, Conicet, Buenos Aires, Argentina
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  • María I. Keller Sarmiento,

    1. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina, Buenos Aires, Argentina,
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  • Darío A. Estrin,

    1. Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, piso 3, Universidad de Buenos Aires, Conicet, Buenos Aires, Argentina
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  • Ruth E. Rosenstein

    1. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina, Buenos Aires, Argentina,
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Ruth E. Rosenstein Departamento de Bioquímica Humana, Facultad de Medicina, UBA, Paraguay 2155, 5°P, (1121), Buenos Aires, Argentina. E-mail: ruthr@fmed.uba.ar

Abstract

In the present work, the effect of melatonin on the hamster retinal nitridergic pathway was examined. When the retinas were incubated in the presence of low concentrations (1 pM–10 nM) of melatonin for 15 min, a significant decrease of nitric oxide synthase (NOS) activity was observed. However, when crude retinal homogenates were preincubated with melatonin for 15 min, no changes in NOS activity were detected, despite the fact that under the same conditions trifluoperazine, a calmodulin inhibitor, significantly decreased enzymatic activity. Kinetic analysis showed that melatonin decreased the Vmax of retinal NOS without changes in the Km. On the other hand, low concentrations (100 pM) of melatonin significantly reduced retinal L-arginine influx. A decrease in the Vmax of L-arginine uptake was observed in the presence of melatonin, whereas the Km remained unchanged. Melatonin significantly inhibited the accumulation of cyclic guanosine monophosphate (cGMP) levels induced by both L-arginine and sodium nitroprusside (SNP). In summary, the present results indicate that melatonin could be a potent inhibitor of the retinal nitridergic pathway.

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