离体小鼠胃肠道对河豚毒素的结肠特异性收缩反应

Y. Okuno, T. Kondo, A. Saeki, E. Uchida, H. Teraoka, T. Kitazawa
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引用次数: 10

摘要

河豚毒素(TTX)是区分离体内脏器官对药物的神经和肌源性反应的有用药理学工具。虽然TTX一般不影响平滑肌张力,但在本研究中,我们发现TTX引起小鼠结肠收缩。本研究的目的是表征这种ttx诱导的小鼠胃肠道收缩。2 .胃和小肠纵向和圆形肌条对TTX的敏感性较低。然而,TTX收缩了近端结肠和远端结肠的平滑肌条。3 TTX、n ω-硝基-l-精氨酸甲酯(l-NAME)、(1)H-[1,2,4]恶二唑[4,3-a]喹诺沙林-1-酮(ODQ)和apamin预处理可抑制TTX诱导的收缩。l-NAME、ODQ或维生素a本身引起结肠收缩,而不是胃和小肠条收缩。l-NAME、ODQ和apamine诱导的收缩的区域依赖性与ttx诱导的收缩相关。l-精氨酸抑制结肠肌条的收缩力,而d-精氨酸不影响其他部位肌条的收缩力。硝普钠引起结肠条带的强烈松弛。1,1-二甲基-4-苯基哌嗪(DMPP)引起近端和远端结肠松弛,l-NAME或apamin显著降低。综上所述,在小鼠胃肠道制剂中,TTX通过阻断强效强直抑制性神经流出来优先诱导结肠条收缩,这涉及到氮能和氨基敏感通路。结肠对l-精氨酸、l-NAME、ODQ和维生素d的特异性反应支持了肠抑制神经元持续抑制结肠运动的假设。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Colon-specific contractile responses to tetrodotoxin in the isolated mouse gastrointestinal tract

1 Tetrodotoxin (TTX) is a useful pharmacological tool for distinguishing neural and myogenic responses of isolated visceral organs to drugs. Although TTX does not generally affect smooth muscle tonus, in this study, we have found that TTX causes contraction of the mouse colon. The aim of this study was to characterize this TTX-induced contraction in the mouse gastrointestinal tract.

2 Longitudinal and circular muscle strips from the stomach and small intestine were less sensitive to TTX. However, TTX contracted both smooth muscle strips from the proximal colon and distal colon.

3 Pretreatment with TTX, Nω-nitro-l-arginine methyl ester (l-NAME), (1)H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and apamin inhibited the TTX-induced contraction. l-NAME, ODQ or apamin itself caused contraction in the colon but not in the gastric and small intestinal strips. Region dependency of l-NAME, ODQ and apamin-induced contraction correlated with that of TTX-induced contraction.

4 l-Arginine but not d-arginine inhibited contractility of the colonic strips without affecting the contractility of muscle strips from other regions. Sodium nitroprusside caused strong relaxation of the colonic strips.

5 1,1-Dimethyl-4-phenylpiperazinium (DMPP) caused relaxation of proximal and distal colons, which was significantly decreased by l-NAME or apamin.

6 In conclusion, among mouse gastrointestinal preparations, TTX induces contraction of colonic strips preferentially through blockade of potent tonic inhibitory neural outflow, which involves nitrergic and apamin-sensitive pathways. Colon-specific responses to l-arginine, l-NAME, ODQ and apamin support the hypothesis that there is a continuous suppression of colonic motility by enteric inhibitory neurons.

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