Hydrogen sulfide: from physiology to pharmacology

Gaseous neutroasmitters are a growing family of enzimatically generated gaseous mediators that exert regulatory functions in mammals. It is now widely recognized that hydrogen sulfide (H(2)S), 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 H(2)S from L-cysteine is catalysed primarily by two enzymes, cystathionine γ-lyase and cystathionine β-synthase. Evidence is accumulating to demonstrate that H(2)S delivered exogenously exerts beneficial effects in animal models of inflammation and pain highlighting the potential for the therapeutic exploitation of H(2)S. Several hybrids have been developed coupling an H(2)S-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 H(2)S has also been exploited for generating anti-platelets and anti-inflammatory agents that inhibit cyclo-oxygenases while sparing the gastrointestinal and cardiovascular tract.