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H 2 S modulates duodenal motility in male rats via activating TRPV 1 and K ATP channels
Author(s) -
Lu Wen,
Li Jing,
Gong Liping,
Xu Xiaomeng,
Han Ting,
Ye Yanfang,
Che Tongtong,
Luo Yan,
Li Jingxin,
Zhan Renzhi,
Yao Wei,
Liu Kejing,
Cui Shuang,
Liu Chuanyong
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12562
Subject(s) - capsazepine , trpv1 , chemistry , medicine , endocrinology , tetrodotoxin , myenteric plexus , trpv , glibenclamide , channel blocker , excitatory postsynaptic potential , transient receptor potential channel , biology , biochemistry , inhibitory postsynaptic potential , receptor , calcium , immunohistochemistry , diabetes mellitus
Background and Purpose H 2 S induces vasodilatation by opening K ATP channels but it may also affect other ion channels. The aim of this study was to investigate the effect of H 2 S on intestinal motility in rats and its underlying mechanism. Experimental Approach The tension of intestinal muscle strips, afferent firing of intestinal mesenteric nerves, length of duodenal smooth muscle cells and whole‐cell membrane potential of dorsal root ganglion ( DRG ) neurons were monitored. H 2 S‐producing enzymes were located by immunofluorescence staining. Key results NaHS exerted early transient excitation and late long‐lasting inhibition on the intestinal contraction. The excitation was attenuated by TRPV1 antagonists capsazepine, A 784168, SB ‐366791 and NK 1 receptor antagonist L 703606, while the inhibition was attenuated by glibenclamide. NaHS increased duodenal afferent nerve firing and depolarized DRG neurons. These effects were reduced by capsazepine and A 784168. NaHS relaxed isolated duodenal smooth muscle cells. The K ATP channels were expressed in smooth muscle cells. Cystathionine β‐synthase and cystathionine γ‐lyase were expressed in rat duodenal myenteric neurons. L ‐cysteine and S‐adenosyl‐L‐methionine increased the contraction of duodenal muscle strips, an effect attenuated by capsazepine and L 703606. Conclusions and Implications NaHS induces biphasic effects on intestinal motility in rats while endogenous H 2 S only exerts an excitatory effect. This transient excitatory effect might be mediated by activation of TRPV1 channels in sensory nerve terminals with the consequent release of substance P . The long‐lasting inhibitory effect might be mediated by activation of K ATP channels in the smooth muscle cells. These findings reveal a novel mechanism for the excitatory effect of H 2 S on gastrointestinal motility.