Hydrogen Sulfide: From Physiology to Pharmacology

Stefano      Fiorucci

Abstract

Gaseous neurotransmitters are a growing family of enzimatically generated gaseous mediators that exert regulatory functions in mammals. It is now widely recognized that hydrogen sulfide (H2S), along with nitric oxide (NO) and carbon monoxide (CO), is an important signaling molecule in cardiovascular, nervous, gastrointestinal, liver and lung physiology and pharmacology. The production of H2S from L-cysteine is catalysed primarily by two enzymes, cystathionine-γ-lyase and cystathionine β-synthase. Evidence is accumulating to demonstrate that H2S delivered exogenously exerts beneficial effects in animal models of inflammation and pain highlighting the potential for the therapeutic exploitation of H2S. Several hybrids have been developed coupling an H2S-releasing moiety to conventional drugs. These molecular hybrids are currently evaluated for efficacy in animal models of gastrointestinal, cardiovascular and neurogical disorders and erectile dysfunction. The anti-inflammatory activity of H2S has also been exploited for generating anti-platelets and anti-inflammatory agents that inhibit cyclo-oxygenases while sparing the gastrointestinal and cardiovascular tract.

Keywords: Hydrogen sulphide, nitric oxide, carbon monoxide, gasotransmitters, cystathionine-β-synthase or cystathione-γ-lyase, vasorelaxation, neuromodulation, cytoprotection, nociception