Hydrogen Sulfide: From Brain to Gut

Three hundred years have passed since the first description of the toxicity of hydrogen sulfide (H2S). Three papers in 1989 and 1990 described relatively high concentrations of sulfide in the brain. In 1996 we demonstrated that cystathionine beta-synthase (CBS) is a H2S producing enzyme in the brain and that H2S enhances the activity of NMDA receptors and facilitates the induction of hippocampal long-term potentiation (LTP), a synaptic model of memory. In the following year, we demonstrated that another H2S producing enzyme, cystathionine g-lyase is in the thoracic aorta, portal vein, and the ileum, and that H2S relaxes these tissues. Based on these observations we proposed H2S as a neuromodulator as well as a smooth muscle relaxant. We recently demonstrated that the third H2S-producing enzyme, 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT) produces H2S in the brain as well as in vascular endothelium. Various functions in many tissues have been proposed. H2S protects neurons and cardiac muscle from oxidative stress. H2S has pro-and anti-inflammatory effects, nociceptive effects, the regulatory function of insulin release, and is even involved in longevity. Recent progress in the studies of physiological functions of H2S in neurons and smooth muscle was described. Antioxid. Redox Signal. 12, 1111-1123.