The possible role of hydrogen sulfide as an endogenous neuromodulator

J Neurosci. 1996 Feb 1;16(3):1066-71. doi: 10.1523/JNEUROSCI.16-03-01066.1996.


Hydrogen sulfide (H2S), which is well known as a toxic gas, is produced endogenously from L-cysteine in mammalian tissues. H2S is present at relatively high levels in the brain, suggesting that it has a physiological function. Two other gases, nitric oxide and carbon monoxide, are also endogenously produced and have been proposed as neuronal messengers in the brain. In this work we show the following: (1) an H2S-producing enzyme, cystathionine beta-synthase (CBS), is highly expressed in the hippocampus; (2) CBS inhibitors hydroxylamine and amino-oxyacetate suppress the production of brain H2S; and (3) a CBS activator, S-adenosyl-L-methionine, enhances H2S production, indicating that CBS contributes to the production of endogenous H2S. We also show that physiological concentrations of H2S selectively enhance NMDA receptor-mediated responses and facilitate the induction of hippocampal long-term potentiation. These observations suggest that endogenous H2S functions as a neuromodulator in the brain.

Publication types

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

MeSH terms

  • Aminooxyacetic Acid / pharmacology
  • Animals
  • Brain Chemistry*
  • Cystathionine beta-Synthase / metabolism*
  • Electric Stimulation
  • Excitatory Amino Acid Agonists / pharmacology
  • Hippocampus / metabolism*
  • Hydrogen Sulfide* / metabolism
  • Hydrogen Sulfide* / pharmacology
  • Hydroxylamine
  • Hydroxylamines / pharmacology
  • Long-Term Potentiation / drug effects
  • Nerve Tissue Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / agonists
  • S-Adenosylmethionine / pharmacology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Excitatory Amino Acid Agonists
  • Hydroxylamines
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Aminooxyacetic Acid
  • Hydroxylamine
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • S-Adenosylmethionine
  • Cystathionine beta-Synthase
  • Hydrogen Sulfide