Physiological concentrations of melatonin inhibit the nitridergic pathway in the Syrian hamster retina.
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 V(max) of retinal NOS without changes in the K(m). On the other hand, low concentrations (100 pM) of melatonin significantly reduced retinal L-arginine influx. A decrease in the V(max) of L-arginine uptake was observed in the presence of melatonin, whereas the K(m) 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.
Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina, Buenos Aires, Argentina.
Daniel A
DA
Sáenz
Adrián G
AG
Turjanski
Geraldine B
GB
Sacca
Marcelo
M
Marti
Fabio
F
Doctorovich
María I Keller
MI
Sarmiento
Darío A
DA
Estrin
Ruth E
RE
Rosenstein
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D006224:Cricetinae; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D008647:Mesocricetus; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D014268:Trifluoperazine / Q000494:pharmacology
D020030:Nitric Oxide Donors; D009599:Nitroprusside; D014268:Trifluoperazine; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D008550:Melatonin