H2S, a novel gasotransmitter, involves in gastric accommodation.

The stomach has variety of functions including reservoir functions. Disorders of the reservoir functions result in symptoms of early satiety and anorexia, which are the major symptoms of patients with functional dyspepsia (FD). Gastric accommodation consists of two types of relaxation: the receptive relaxation and the adaptive relaxation. These physiological responses are important to accommodate the intake of food and liquid. Adaptive relaxation is a reflex in which the fundus of the stomach dilates in response to small increases in intragastric pressure when food enters the stomach. Receptive relaxation is a reflex in which the gastric fundus dilates when food passes down the pharynx and the esophagus. Some gastrointestinal hormones and chemical mediators such as gastrin, histamine1, serotonin, vasoactive intestinal peptide (VIP)2 and nitric oxide (NO)3,4,5 have been shown to mediate these two types of relaxations. In the gastrointestinal tract, NO is an important non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmitter which is released in response to nerve stimulation and relaxes smooth muscles6,7. Animal studies have consistently shown that basal tone is decreased by vagal stimulation and that this effect is blocked by the NO inhibitor8,9,10,11. Besides NO and CO, hydrogen sulfide (H2S) is the third gasotransmitter. H2S is produced mainly by two enzymes:cystathionine–β–synthase (CBS) and cystathionine-γ–lyase (CSE), using L-cysteine (L-Cys) as the substrate12,13,14. CBS and CSE are expressed in the enteric nervous system (ENS)15. In the gastrointestinal tract, sodium hydrogen sulfide (NaHS), a source of H2S, can reduce spontaneous or acetylcholine (ACh)-induced contraction of ileal smooth muscles16,17. H2S also causes concentration-dependent relaxation of pre-contracted smooth muscles in the mouse gastric fundus and distal colon18,19. Muscle contractions of the mouse colon and jejunum were also inhibited by application of NaHS20. H2S is similar with the two kinds of endogenous gas signal molecules of CO and NO, they are very important bio-regulating substances, and share some common characteristics. We hypothesize that beside NO, H2S is another gasotransmitter which involves in the mechanical accommodation of the stomach. In the present study, we therefore examined the role of H2S in receptive and adaptive relaxation of the mouse stomach.