H2S, a novel gasotransmitter, involves in gastric accommodation.

Ailin Xiao,Chuanyong Liu,Jianqiang Guo,Jingxin Li,Xin Lu,Hongjuan Wang,Tonghui Xu,Jianchun Zhu,Di Huang

doi:10.1038/srep16086

Ailin Xiao, Chuanyong Liu + Show 7 more

Open Access

https://doi.org/10.1038/srep16086

Copy DOI

Abstract

H2S 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 H2S in gastric accommodation using CBS+/− mice, immunohistochemistry, immunoblot, methylene blue assay, intragastric pressure (IGP) recording and electrical field stimulation (EFS). Mouse gastric fundus expressed H2S-generating enzymes (CBS and CSE) and generated detectable amounts of H2S. The H2S 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 H2S 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 H2S was found in patients with functional dyspepsia (FD). In conclusion, endogenous H2S, a novel gasotransmitter, involves in gastric accommodation.

Highlights

Molecules of CO and NO, they are very important bio-regulating substances, and share some common characteristics
CBS and CSE have been documented to be expressed in certain neurons of the mouse[21], rat[22], guinea-pig and human enteric nervous systems[15]
We demonstrated that both H2S generating enzymes exist in gastric fundus from mouse or human

Summary

Introduction

Molecules of CO and NO, they are very important bio-regulating substances, and share some common characteristics. CBS and CSE were expressed in mice fundus as demonstrated by Western blot studies (Fig. 1a). The immunohistochemistry study shows that CBS was expressed on the soma of the myenteric neurons of gastric fundus muscle myenteric plexus (Fig. 1b). The biosynthesis of H2S was increased by 3- fold over basal values after incubation of tissue homogenates with L-Cys, the CBS/CSE substrate (Fig. 1c).

Results

Conclusion