title: H2S-induced gastric fundus smooth muscle tension potentiation is mediated by the phosphoinositide 3-kinase/Akt/endothelial nitric oxide synthase pathway.
abstract: What is the central question of this study? The present study investigated the relationship between H2S and NO in regulation of gastric fundus tension. What is the main finding and its importance? Endogenous or exogenous H2S and NO have opposite effects on fundus tension, and H2S-induced gastric fundus tension enhancements are mediated by inhibition of NO generation through the phosphoinositide 3-kinase/Akt pathway. These results are very important in exploring the mechanism of physiological accommodation and accommodation disorder. Hydrogen sulphide (H2S) is considered a new gasotransmitter, along with NO and CO. It was recently confirmed that H2S and NO play important roles in the regulation of gastrointestinal smooth muscle tension. The present study was designed to elucidate the interactions between H2S and NO with respect to the regulation of gastric fundus smooth muscle tension using Western blotting, physiological and electrochemical techniques. Real-time H2S and NO generation was detected in gastric smooth muscle tissue. NaHS, an H2S donor, enhanced fundus smooth muscle tension, whereas SNP, an NO donor, decreased fundus smooth muscle tension in a dose-dependent manner. NaHS-induced increases in fundus smooth muscle tension were suppressed by l-NAME, an NO synthase inhibitor. Aminooxyacetic acid (AOAA), a cystathionine β-synthase inhibitor, exerted inhibitory effects on fundus smooth muscle tension; these effects were also suppressed by l-NAME. Real-time NO generation was significantly potentiated by AOAA. Endothelial nitric oxide synthase (eNOS) phosphorylation at serine 1177 and Akt phosphorylation at serine 308 and threonine 473 were significantly inhibited by NaHS. LY294002, a phosphoinositide 3-kinase inhibitor, blocked these NaHS-mediated effects. However, eNOS phosphorylation at serine 1177 and Akt phosphorylation at serine 308 and threonine 473 were significantly potentiated by AOAA. Cystathionine β-synthase siRNA interference significantly increased eNOS phosphorylation at serine 1177 and Akt phosphorylation at serine 308 and threonine 473. Cystathionine β-synthase siRNA interference also increased total eNOS protein expression levels but did not significantly change total Akt kinase protein expression levels. These results suggest that H2S-induced enhancement of gastric fundus tension is mediated by inhibition of NO generation through the phosphoinositide 3-kinase/Akt pathway.
authors.affiliation: Department of Physiology, College of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China.
authors.forename: Xiang-Min
authors.initials: XM
authors.lastname: Meng
authors.affiliation: Department of Physiology, College of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Physiology, College of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Lu
authors.affiliation: Department of Physiology, College of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Chungbuk National University College of Medicine, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, Affiliated to Shanghai JiaoTong University School of Medicine, 1665 Kong Jiang Road, 200092, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Physiology, College of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, China.
authors.forename: Wen-Xie
authors.identifier: 0000-0003-3040-4340
authors.initials: WX
authors.lastname: Xu
mesh_terms: D000818:Animals; D005748:Gastric Fundus / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D006862:Hydrogen Sulfide
keywords: H2S; NO; PI3K/Akt; gastric fundus tension