Strong inhibition of neuronal nitric oxide synthase by the calmodulin antagonist and anti-estrogen drug tamoxifen

Biochem Pharmacol. 1997 Nov 15;54(10):1109-14. doi: 10.1016/s0006-2952(97)00316-x.

Abstract

The anti-estrogen drug tamoxifen (TMX) was found to act as a strong inhibitor of purified neuronal nitric oxide synthase (nNOS) (IC50 = 2 +/- 0.5 microM), whereas it was inactive toward inducible macrophage NOS (IC50 > 100 microM). TMX affected the activation of NOS by calmodulin, as it not only inhibited L-arginine oxidation to nitric oxide and L-citrulline but also NADPH oxidation and calmodulin-dependent cytochrome c reduction catalyzed by nNOS. These results suggest that TMX could exert some of its biological effects by interfering with constitutive NOS-dependent formation of nitric oxide and/or superoxide ion in various tissues.

MeSH terms

  • Animals
  • Calmodulin / antagonists & inhibitors*
  • Enzyme Inhibitors / pharmacology*
  • Estrogen Antagonists / pharmacology*
  • Mice
  • Mice, Inbred C3H
  • Neurons / enzymology*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase Type I
  • Rats
  • Tamoxifen / pharmacology*

Substances

  • Calmodulin
  • Enzyme Inhibitors
  • Estrogen Antagonists
  • Tamoxifen
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, mouse
  • Nos1 protein, rat