Different regulatory effects of hydrogen sulfide and nitric oxide on gastric motility in mice

• Published in: European journal of pharmacology Vol. 720; no. 1-3; pp. 276 - 285
• Main Authors: Huang, Xu, Meng, Xiang-Min, Liu, Dong-Hai, Wu, Yi-Song, Guo, Xin, Lu, Hong-Li, Zhuang, Xue-Yan, Kim, Young-chul, Xu, Wen-Xie
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2013
• Subjects: Alkynes - pharmacology; Aminooxyacetic Acid - pharmacology; Animals; Cystathionine beta-Synthase - antagonists & inhibitors; Cystathionine beta-Synthase - physiology; Cystathionine gamma-Lyase - antagonists & inhibitors; Cystathionine gamma-Lyase - physiology; Endogenous H2S; Endogenous NO; Gastric antral smooth muscle; Gastrointestinal Motility - drug effects; Glycine - analogs & derivatives; Glycine - pharmacology; Hydrogen Sulfide - pharmacology; Male; Mice; Mice, Inbred ICR; Motility; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - pharmacology; Nitric Oxide Donors - pharmacology; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - physiology; Nitric Oxide Synthase Type III - antagonists & inhibitors; Nitric Oxide Synthase Type III - physiology; Nitroprusside - pharmacology; Stomach - drug effects; Stomach - physiology; Sulfides - pharmacology; Motility; Endogenous H2S; Gastric antral smooth muscle; Endogenous NO; Endogenous HS
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2013.10.017

NO and H2S are gaseous signaling molecules that modulate smooth muscle motility. We aimed to identify expressions of enzymes that catalyze H2S and NO generation in mouse gastric smooth muscle, and determine relationships between endogenous H2S and NO in regulation of smooth muscle motility. Western blotting and immunocytochemistry methods were used to track expressions of neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in gastric smooth muscles. Smooth muscle motility was recorded by isometric force transducers. cGMP production was measured by a specific radioimmunoassay. We found that CBS, CSE, eNOS, and nNOS were all expressed in mice gastric antral smooth muscle tissues, and in cultured gastric antral smooth muscle cells. AOAA significantly inhibited smooth muscle contractions in the gastric antrum, which was significantly recovered by NaHS, while PAG had no significant effect. l-NAME enhanced contractions. NaHS at low concentrations increased basal tension but decreased it at high concentrations. SNP significantly inhibited the contractions, which could be recovered by NaHS both in the absence and presence of CuSO4. ODQ did not block NaHS-induced excitatory effect, while IBMX partially blocked this effect. cGMP production in smooth muscle was significantly increased by SNP but was not affected by NaHS. All these results suggest that endogenous H2S and NO appear to play opposite roles in regulating gastric motility and their effects may be via separate signal transduction pathways. Intracellular H2S/NO levels may be maintained in a state of balance to warrant normal smooth muscle motility.