Department of Physiology, Shandong University School of Medicine, Jinan, China.
Br J Pharmacol. 2014 Mar;171(6):1534-50. doi: 10.1111/bph.12562.
H2 S induces vasodilatation by opening KATP channels but it may also affect other ion channels. The aim of this study was to investigate the effect of H2 S on intestinal motility in rats and its underlying mechanism.
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. H2 S-producing enzymes were located by immunofluorescence staining.
NaHS exerted early transient excitation and late long-lasting inhibition on the intestinal contraction. The excitation was attenuated by TRPV1 antagonists capsazepine, A784168, SB-366791 and NK1 receptor antagonist L703606, while the inhibition was attenuated by glibenclamide. NaHS increased duodenal afferent nerve firing and depolarized DRG neurons. These effects were reduced by capsazepine and A784168. NaHS relaxed isolated duodenal smooth muscle cells. The KATP 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 L703606.
NaHS induces biphasic effects on intestinal motility in rats while endogenous H2 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 KATP channels in the smooth muscle cells. These findings reveal a novel mechanism for the excitatory effect of H2 S on gastrointestinal motility.
H2S 通过开放 KATP 通道引起血管舒张，但它也可能影响其他离子通道。本研究旨在探讨 H2S 对大鼠肠道动力的影响及其潜在机制。
监测肠肌条的张力、肠肠系膜神经传入放电、十二指肠平滑肌细胞长度和背根神经节（DRG）神经元的全细胞膜电位。通过免疫荧光染色定位 H2S 产生酶。
NaHS 对肠收缩早期产生短暂兴奋，晚期产生持久抑制。兴奋被 TRPV1 拮抗剂辣椒素、A784168、SB-366791 和 NK1 受体拮抗剂 L703606 减弱，而抑制被格列本脲减弱。NaHS 增加十二指肠传入神经放电并使 DRG 神经元去极化。这些作用被辣椒素和 A784168 减弱。NaHS 使离体十二指肠平滑肌松弛。KATP 通道在平滑肌细胞中表达。胱硫醚β-合酶和胱硫醚γ-裂解酶在大鼠十二指肠肌间神经元中表达。L-半胱氨酸和 S-腺苷-L-蛋氨酸增加十二指肠肌条的收缩，这种作用被辣椒素和 L703606 减弱。
NaHS 对大鼠肠道动力产生双相作用，而内源性 H2S 仅产生兴奋作用。这种短暂的兴奋作用可能是通过感觉神经末梢 TRPV1 通道的激活介导的，随之而来的是 P 物质的释放。持久的抑制作用可能是通过平滑肌细胞中 KATP 通道的激活介导的。这些发现揭示了 H2S 对胃肠道动力的兴奋作用的新机制。
