Colon-specific contractile responses to tetrodotoxin in the isolated mouse gastrointestinal tract
Colon-specific contractile responses to tetrodotoxin in the isolated mouse gastrointestinal tract
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DOI：
10.1111/j.1474-8673.2011.00462.x
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发表时间：
2011-01-01
期刊：
影响因子：
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通讯作者：
Kitazawa, T.
中科院分区：
文献类型：
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作者：
Okuno, Y.;Kondo, T.;Kitazawa, T.
P>1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一般不会影响平滑肌张力，但在这项研究中，我们发现TTX会导致小鼠结肠收缩。本研究的目的是描述TTX诱导的小鼠胃肠道收缩。2胃和小肠的纵向和环形肌条对TTX不太敏感。TTX、N ω-硝基-L-精氨酸甲酯（l-NAME）、（1）H-[1，2，4]恶二唑并[4，3-a]喹喔啉-1-酮（ODQ）和apamin预处理可抑制TTX诱导的平滑肌收缩。L-NAME、ODQ或apamin本身引起结肠收缩，但不引起胃和小肠条收缩。L-NAME、ODQ和apamin诱导的收缩的区域依赖性与TTX诱导的收缩相关。4 l-精氨酸而不是d-精氨酸抑制结肠条的收缩性，而不影响其他区域的肌条的收缩性。硝普钠引起结肠条的强烈松弛。5 1，1-二甲基-4-苯基哌嗪（DMPP）引起近端和远端结肠的松弛，l-NAME或apamin显著降低。6总之，在小鼠胃肠道制剂中，TTX优先通过阻断强效紧张性抑制性神经流出（涉及氮能和apamin敏感性通路）诱导结肠条收缩。对l-精氨酸、l-NAME、ODQ和apamin的结肠特异性反应支持肠抑制性神经元持续抑制结肠运动的假设。
P>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, N omega-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.