Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, 710004, Xi'an, Shaanxi, China; Shaanxi Province Key Laboratory of Gastrointestinal Motility Disorders,710004, Xi'an, Shaanxi, China.
Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei Province, China.
J Pharmacol Sci. 2022 Jul;149(3):100-107. doi: 10.1016/j.jphs.2022.04.004. Epub 2022 Apr 21.
HS is a well-known relaxant regulator in muscle contraction but little attention has been paid to its excitatory effect on colonic motility. To investigate the excitation of HS on rat colonic contraction and the underlying mechanism, the muscle contractile activity was assessed by an organ bath system, the level of substance P (SP) in the colon was detected using enzyme immunoassay kits, L-type Ca channel currents (I) and large conductance Ca-activated K channel currents (I) in smooth muscle cells (SMCs) were measured by patch-clamp electrophysiology. The results show that the HS donor NaHS (100 μM) reversed the relaxation of the NO donor SNP on colonic muscle contraction. Pretreatment with the TRPV1 antagonist and the neurokinin receptor antagonists attenuated the NaHS-induced excitation. Incubation of colon with NaHS increased the SP level. In freshly isolated SMCs, NaHS exerted a biphasic effect on I and concentration-dependently inhibited the I. And 100 μM NaHS partially reversed the SNP-induced changes in I and I. We concluded that exogenous HS exerts a potential excitatory effect on colonic motility, which may be achieved by activating SP release from afferent nerves in combination with a direct activation of I and suppression of I in SMCs.
HS 是一种众所周知的肌肉收缩松弛调节剂，但人们对其对结肠运动的兴奋作用关注甚少。为了研究 HS 对大鼠结肠收缩的兴奋作用及其潜在机制，我们采用器官浴系统评估肌肉收缩活性，使用酶联免疫吸附试剂盒检测结肠中 P 物质（SP）的水平，通过膜片钳电生理学测量平滑肌细胞（SMCs）中的 L 型钙通道电流（I）和大电导钙激活钾通道电流（I）。结果表明，HS 供体 NaHS（100 μM）逆转了 NO 供体 SNP 对结肠肌肉收缩的松弛作用。TRPV1 拮抗剂和神经激肽受体拮抗剂预处理可减弱 NaHS 诱导的兴奋。用 NaHS 孵育结肠可增加 SP 水平。在新鲜分离的 SMCs 中，NaHS 对 I 产生双相作用，并浓度依赖性地抑制 I。100 μM NaHS 部分逆转了 SNP 诱导的 I 和 I 的变化。我们得出结论，外源性 HS 对结肠运动具有潜在的兴奋作用，这可能是通过激活传入神经释放 SP 与直接激活 SMCs 中的 I 和抑制 I 来实现的。
