Gaseous Mediators Nitric Oxide and Hydrogen Sulfide in the Mechanism of Gastrointestinal Integrity, Protection and Ulcer Healing

Nitric oxide (NO) and hydrogen sulfide (H(2)S) are known as biological messengers; they play an important role in human organism and contribute to many physiological and pathophysiological processes. NO is produced from l-arginine by constitutive NO synthase (NOS) and inducible NOS enzymatic pathways. This gaseous mediator inhibits platelet aggregation, leukocyte adhesion and contributes to the vessel homeostasis. NO is known as a vasodilatory molecule involved in control of the gastric blood flow (GBF) and the maintenance of gastric mucosal barrier integrity in either healthy gastric mucosa or that damaged by strong irritants. Biosynthesis of H(2)S in mammals depends upon two enzymes cystathionine-β-synthase and cystathionine γ-lyase. This gaseous mediator, similarly to NO and carbon monoxide, is involved in neuromodulation, vascular contractility and anti-inflammatory activities. For decades, H(2)S has been known to inhibit cytochrome c oxidase and reduce cell energy production. Nowadays it is generally considered to act through vascular smooth muscle ATP-dependent K(+) channels, interacting with intracellular transcription factors and promote sulfhydration of protein cysteine moieties within the cell, but the mechanism of potential gastroprotective and ulcer healing properties of H(2)S has not been fully explained. The aim of this review is to compare current results of the studies concerning the role of H(2)S and NO in gastric mucosa protection and outline areas that may pose new opportunities for further development of novel therapeutic targets.