Hydrogen Sulfide as a Neuromodulator

Abstract

Hydrogen sulfide (H₂S) is a well-known toxic gas with the smell of rotten eggs. Since the first description of the toxicity of H₂S in 1713, most studies about H₂S have been devoted to its toxic effects. Recently, H₂S has been proposed as a physiologically active messenger. Three groups discovered that the brain contains relatively high concentrations of endogenous H₂S. This discovery accelerated the identification of an H₂S-producing enzyme, cystathionine β-synthase (CBS) in the brain. In addition to the well-known regulators for CBS, S-adenosyl-L-methionine (SAM) and pyridoxal-5′-phosphate, it was recently found that Ca²⁺/calmodulin-mediated pathways are involved in the regulation of CBS activity. H₂S is produced in response to neuronal excitation, and alters hippocampal long-term potentiation (LTP), a synaptic model for memory. can also regulate the release of corticotropin-releasing hormone (CRH) from hypothalamus. Another H₂S producing enzyme, cystathionine γ-lyase (CSE), has been identified in smooth muscle, and H₂S relaxes smooth muscle in synergy with nitric oxide (NO). Recent progress in the study of H₂S as a novel neuromodulator/transmitter in the brain is briefly reviewed.