Physiological concentrations of melatonin inhibit nitric oxide synthase in rat cerebellum.
In the present paper we show the inhibitory effect of melatonin on rat cerebellar nitric oxide synthase (NOS) activity. NO production was monitored by the stoichiometric conversion of L-arginine to L-citrulline. The inhibitory effect of melatonin was dose-dependent, with an IC50 value of about 0.1 mM. However, a significant inhibition of enzyme activity (> 22%) was observed at 1 nM melatonin which is in the range of the physiological serum concentration of the hormone at night. The inhibitory effect of melatonin was observed exclusively in the presence of Ca++. Results suggest a new and important role of the pineal hormone melatonin on central nervous system processes, i.e., by modulating NO production.
Pozo
D
D
Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine, Spain.
Reiter
R J
RJ
Calvo
J R
JR
Guerrero
J M
JM
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology*; D002956:Citrulline / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D051381:Rats
D002956:Citrulline; D004533:Egtazic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D008550:Melatonin; D002118:Calcium