H2S, a novel gasotransmitter, involves in gastric accommodation

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.

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

“…Taken together, although various screening efforts have identified many different CBS inhibitors, for most pharmacological studies (both in vitro and in vivo) AOAA remains the compound of choice; it has been used in a large number of publications over the last decade. The basic physiological papers include mechanistic studies investigating the role of endogenous H 2 S on various channels and cellular processes (e.g., Donovan et al, 2011;Gil et al, 2011;Roy et al, 2012;Martinez-Cutillas et al, 2015;Rios et al, 2015;Xiao et al, 2015;Krause et al, 2016;Liu et al, 2016d;Rios et al, 2016;Yan et al, 2016;Yetik-Anacak et al, 2016). Many of these reports are in the area of cancer, where they show the antiproliferative effects of this compound and as additive or synergistic antitumor effects in combination with various chemotherapeutic agents (Szabo et al, 2013;Bhattacharyya et al, 2013;Módis et al, 2014b;Szczesny et al, 2016).…”

Hydrogen sulfide suppresses ghrelin secretion in vitro and delays postprandial ghrelin secretion while reducing appetite in mice

“…Alternatively, some recent work has implicated the other predominant H 2 S producing enzyme, CBS, in the stomach (Xiao et al. ). An examination of the effects of CBS inhibitors on ghrelin levels would clarify the potential role of this enzyme in ghrelin regulation.…”

l‐Cysteine enhances nutrient absorption via a cystathionine‐β‐synthase‐derived H2S pathway in rodent jejunum

“…The rate of tissue H 2 S production was measured as described previously . Briefly, male Wistar rats were killed by dislocation of the cervical spine.…”