Physiological concentrations of melatonin inhibit nitric oxide synthase in rat cerebellum

Life Sci. 1994;55(24):PL455-60. doi: 10.1016/0024-3205(94)00532-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors*
  • Animals
  • Arginine / metabolism
  • Calcium / pharmacology
  • Cerebellum / drug effects
  • Cerebellum / enzymology*
  • Citrulline / metabolism
  • Dose-Response Relationship, Drug
  • Egtazic Acid / pharmacology
  • Female
  • In Vitro Techniques
  • Male
  • Melatonin / pharmacology*
  • Nitric Oxide Synthase
  • Rats


  • Citrulline
  • Egtazic Acid
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Melatonin
  • Calcium