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

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