Hydrogen sulfide is a novel prosecretory neuromodulator in the guinea-pig and human colon
Hydrogen sulfide is a novel prosecretory neuromodulator in the guinea-pig and human colon
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DOI：
10.1053/j.gastro.2006.08.035
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发表时间：
2006-11-01
期刊：
影响因子：
29.4
通讯作者：
Schemann, Michael
中科院分区：
文献类型：
--
作者：
Schicho, Rudolf;Krueger, Dagmar;Schemann, Michael
背景与目的：硫化氢（H2S）是一种新型的气体中间体。我们探索了它在人类和豚鼠结肠中未知的神经调节作用。研究方法：我们使用免疫组化检测H2S产生酶胱硫醚γ-裂解酶（CSE）和胱硫醚β-合成酶（CBS）在肠神经元，Ussing室测量粘膜离子分泌，和神经成像与电压和Ca++敏感染料记录H2S对豚鼠和人肠神经元的影响。结果：豚鼠和人胃粘膜下和肌间神经元的CSE和CBS共标记率均在90%以上。Cajal肌间质细胞呈CSE免疫反应阳性。外源性H2S供体NaHS（0.2-2.5 mmol/L）浓度依赖性地增加人和豚鼠粘膜下层/粘膜制剂中的氯化物分泌，但在结肠上皮细胞系T84中不增加。河豚毒素（0.5 μ mol/L）、辣椒素脱敏（10 μ mol/L）和瞬时受体电位香草酸I受体拮抗剂辣椒平（10 μ mol/L）均能显著降低细胞的分泌反应。内源性H2S供体L-半胱氨酸也诱导分泌，辣椒素脱敏，CBS抑制剂氨基-氧乙酸和CSE抑制剂炔丙基甘氨酸显着减少。NaHS使23%的豚鼠和36%的人粘膜下神经元的锋电位放电增加，但对培养的豚鼠肠神经元的Ca ~（++）动员没有影响。这种兴奋性反应被辣椒素脱敏和辣椒平显著降低，但不被格列本脲（10 μ mol/L）。结论：在人类和豚鼠肠神经元中存在H2S产生酶，对肠神经元的兴奋作用和NaHS的促分泌作用表明H2S是一种新型的肠道信号分子。其作用主要涉及外源性传入终末上的瞬时受体电位香草酸受体1，其反过来激活肠神经元。
Background & Aims: Hydrogen sulfide (H2S) has been suggested as a novel gasomediator. We explored its unknown neuromodulatory role in human and guinea-pig colon. Methods: We used immunohistochemistry to detect H2S-producing enzymes cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS) in enteric neurons, Ussing chambers to measure mucosal ion secretion, and neuroimaging with voltage-and Ca++-sensitive dyes to record H2S effects on guinea-pig and human enteric neurons. Results: More than 90% of guineapig and human submucous and myenteric neurons were colabeled for CSE and CBS. Myenteric interstitial cells of Cajal were CSE-immunoreactive. The exogenous H2S donor NaHS (0.2-2.5 mmol/L) concentration-dependently increased chloride secretion in human and guinea-pig submucosa/mucosa preparations, but not in the colonic epithelial cell line T84. The secretory response was reduced significantly by tetrodotoxin (0.5 mu mol/L), capsaicin desensitization (10 mu mol/L), and the transient receptor potentials vanilloid receptor I antagonist capsazepine (10 mu mol/L). The endogenous H2S donor L-cysteine also induced secretion that was diminished significantly by capsaicin desensitization, the CBS inhibitor amino-oxyacetic acid, and the CSE inhibitor propargylglycine. NaHS increased spike discharge in 23% of guinea-pig and 36% of human submucous neurons, but had no effect on Ca++ mobilization in cultured guineapig enteric neurons. This excitatory response was reduced significantly by capsaicin desensitization and capsazepine, but not by glibenclamide (10 mu mol/L). Conclusions: The presence of H2S-producing enzymes in human and guineapig enteric neurons, the excitatory action on enteric neurons, and the prosecretory effects of NaHS suggest H2S as a novel gut-signaling molecule. Its action mainly involves transient receptor potentials vanilloid receptor 1 receptors on extrinsic afferent terminals, which in turn activate enteric neurons.