Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO-

Neuron. 1999 Oct;24(2):461-9. doi: 10.1016/s0896-6273(00)80859-4.


Recent evidence indicates that the NO-related species, nitroxyl anion (NO), is produced in physiological systems by several redox metal-containing proteins, including hemoglobin, nitric oxide synthase (NOS), superoxide dismutase, and S-nitrosothiols (SNOs), which have recently been identified in brain. However, the chemical biology of NO- remains largely unknown. Here, we show that NO- -unlike NO*, but reminiscent of NO+ transfer (or S-nitrosylation)- -reacts mainly with Cys-399 in the NR2A subunit of the N-methyl-D-aspartate (NMDA) receptor to curtail excessive Ca2+ influx and thus provide neuroprotection from excitotoxic insults. This effect of NO- closely resembles that of NOS, which also downregulates NMDA receptor activity under similar conditions in culture.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anions / metabolism
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Female
  • N-Methylaspartate / pharmacology
  • Neurons / metabolism
  • Neurotoxins / metabolism*
  • Nitric Oxide / pharmacology
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / metabolism
  • Nitrogen Oxides / metabolism*
  • Oocytes
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / chemistry
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / metabolism
  • Xenopus laevis


  • Anions
  • Neurotoxins
  • Nitric Oxide Donors
  • Nitrogen Oxides
  • Receptors, N-Methyl-D-Aspartate
  • Sulfhydryl Compounds
  • Nitric Oxide
  • N-Methylaspartate
  • Nitric Oxide Synthase
  • nitroxyl