Endogenous production of H₂S in the gastrointestinal tract: Still in search of a physiologic function

Hydrogen sulfide (H₂S) has long been associated with the gastrointestinal tract, especially the bacteria-derived H₂S present in flatus. Along with evidence from other organ systems, the finding that gastrointestinal tissues are capable of endogenous production of H₂S has led to the hypothesis that H₂S is an endogenous gaseous signaling molecule. In this review, the criteria of gasotransmitters are reexamined, and evidence from the literature regarding H₂S as a gaseous signaling molecule is discussed. H₂S is produced enzymatically by gastrointestinal tissues, but evidence is lacking on whether H₂S production is regulated. H₂S causes well-defined physiologic effects in gastrointestinal tissues, but evidence for a receptor for H₂S is lacking. H₂S is inactivated through enzymatic oxidation, but evidence is lacking on whether manipulating H₂S oxidation alters endogenous cell signaling. Remaining questions regarding the role of H₂S as a gaseous signaling molecule in the gastrointestinal tract suggest that H ₂S currently remains a molecule in search of a physiologic function. Antioxid. Redox Signal. 12, 1135-1146.