H ₂S, a novel gasotransmitter, involves in gastric accommodation

Abstract

H ₂S is produced mainly by two enzymes:cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE), using L-cysteine (L-Cys) as the substrate. In this study, we investigated the role of H ₂S in gastric accommodation using CBS ^+/− mice, immunohistochemistry, immunoblot, methylene blue assay, intragastric pressure (IGP) recording and electrical field stimulation (EFS). Mouse gastric fundus expressed H ₂S-generating enzymes (CBS and CSE) and generated detectable amounts of H ₂S. The H ₂S donor, NaHS or L-Cys, caused a relaxation in either gastric fundus or body. The gastric compliance was significantly increased in the presence of L-Cys (1 mM). On the contrary, AOAA, an inhibitor for CBS, largely inhibited gastric compliance. Consistently, CBS ^+/− mice shows a lower gastric compliance. However, PAG, a CSE inhibitor, had no effect on gastric compliances. L-Cys enhances the non-adrenergic, non-cholinergic (NANC) relaxation of fundus strips, but AOAA reduces the magnitude of relaxations to EFS. Notably, the expression level of CBS but not CSE protein was elevated after feeding. Consistently, the production of H ₂S was also increased after feeding in mice gastric fundus. In addition, AOAA largely reduced food intake and body weight in mice. Furthermore, a metabolic aberration of H ₂S was found in patients with functional dyspepsia (FD). In conclusion, endogenous H ₂S, a novel gasotransmitter, involves in gastric accommodation.