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Hydrogen sulfide downregulates colonic afferent sensitivity by a nitric oxide synthase‐dependent mechanism in mice
Author(s) -
Xu Xiaomeng,
Li Shuang,
Shi Yao,
Tang Yan,
Lu Wen,
Han Ting,
Xue Bing,
Li Jingxin,
Liu Chuanyong
Publication year - 2019
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13471
Subject(s) - chemistry , nociception , sodium hydrosulfide , nitric oxide , interstitial cell of cajal , pharmacology , endocrinology , nitric oxide synthase , inhibitory postsynaptic potential , channel blocker , medicine , receptor , hydrogen sulfide , biochemistry , calcium , smooth muscle , sulfur , organic chemistry
Background The effect of hydrogen sulfide (H 2 S) on visceral nociception is elusive. The conflicting evidence of its pro‐ and antinociceptive effects raises a series of questions with respect to the effect of H 2 S on colonic afferent activity and the underlying mechanism, which was further elucidated in this study. Methods Colonic mesenteric afferent nerve spikes of normal male C57BL/6J mice, Cbs +/− mice, and Wistar rats were recorded in vitro. The abdominal withdrawal reflex (AWR) induced by colorectal distension (CRD) was evaluated in Cbs +/− mice and WT littermates. Key Results Sodium hydrosulfide (NaHS) significantly decreased colonic afferent spontaneous discharge, chemosensitivity to bradykinin, mechanosensitivity to ramp distention, and intraluminal pressure in mice. Reducing the relaxant action of NaHS on intestinal smooth muscle using the nonspecific K + channel blocker TEA (10 mmol/L) did not block the inhibition of NaHS on afferent nerve activity. The inhibitory effects of NaHS (0.5 mmol/L) on colonic afferent sensitivity were largely eliminated by the pretreatment with nonspecific NOS inhibitor N G ‐Methyl‐ l ‐arginine acetate salt (1 mmol/L), the specific nNOS inhibitor NPLA (1 μmol/L), or N‐type Ca 2+ channel blocker ω‐conotoxin GVIA (1 μmol/L). Compared with WT mice, Cbs +/− mice showed increased mesenteric afferent sensitivity to colonic distention and enhanced hyperalgesic response to CRD. Intraperitoneal administration of NaHS (60 μmol/kg) alleviated the nociception response to CRD in both Cbs +/− and WT mice. Conclusions and Inferences H 2 S downregulates colonic mesenteric afferent sensitivity by a nNOS‐dependent mechanism in mice. Our findings may demonstrate a new mechanism for the antinociceptive effect of H 2 S in colon.