Role of nitric oxide, vasoactive intestinal polypeptide, and ATP in inhibitory neurotransmission in human jejunum.
Role of nitric oxide, vasoactive intestinal polypeptide, and ATP in inhibitory neurotransmission in human jejunum.
复制标题
一氧化氮、血管活性肠多肽和 ATP 在人空肠抑制性神经传递中的作用。
DOI：
10.1006/jsre.1999.5590
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Sarr,MG
中科院分区：
文献类型：
--
作者：
Murr,MM;Balsiger,BM;Farrugia,G;Sarr,MG
背景人类肠道中的抑制性神经传递知之甚少。本研究旨在确定一氧化氮（NO）、三磷酸腺苷（ATP）和血管活性肠肽（VIP）在人空肠环形肌条抑制性神经传递中的作用。方法在肾上腺素能和胆碱能受体阻断下，评价预收缩（10− 5 M P物质）的正常人空肠肌条对电场刺激（EFS）的体外反应。选择性神经阻滞是通过NO合成酶抑制剂或1-NG-硝基精氨酸甲酯（1-NAME，10− 3 M）、VIP受体拮抗剂（4-Cl-d -Phe 6Leu 17-VIP，10− 7 M）、P2嘌呤能受体阻滞剂苏拉明（3 × 1014 M）或钙依赖性钾通道阻滞剂apamin（10− 6 M）实现的。结果外源性NO和ATP剂量依赖性地抑制收缩活动和松弛肌条，产生50%效应的浓度（ED 50）分别为4.5 ± 2.9 × 10 - 6 M和3.3 ± 1.3 × 10 - 4 M。EFS导致所有组的预收缩肌条松弛。与对照组相比，舒张功能降低，但不能完全消除（2、5和10 Hz时分别为−0.12 ± 0.03 vs − 0.33 ± 0.05、−0.07 ± 0.03 vs −0.34 ± 0.05和0.04 ± 0.03 vs −0.30 ± 0.04，P< 0.011）。（1-NAME的非活性立体异构体）、4-Cl-d -Phe 6Leu 17-VIP、苏拉明和apamin不改变EFS诱导的舒张。我们的研究结果表明，虽然NO在人空肠环行肌的抑制性神经传递中起主导作用，但另一种神经递质似乎也参与其中。这些数据可能会影响理解肠道动力障碍的机制。
BackgroundInhibitory neurotransmission in the human intestine is poorly understood. This study was undertaken to determine the role of nitric oxide (NO), adenosine triphosphate (ATP), and vasoactive intestinal polypeptide (VIP) in inhibitory neurotransmission in human jejunal circular muscle strips.MethodsIn vitroresponse of precontracted (10−5M substance P) normal human jejunal muscle strips to electric field stimulation (EFS) under adrenergic and cholinergic receptor blockade was evaluated. Selective neural blockade was obtained by the NO synthase inhibitorl -NG-nitroarginine methyl ester (l -NAME, 10−3M), VIP receptor antagonist (4-Cl-d -Phe6Leu17-VIP, 10−7M), P2purinergic receptor blocker suramin (3 × 1014M), or the calcium-dependent potassium channel blocker apamin (10−6M). Force generated in response to EFS was quantitated and analyzed statistically.ResultsExogenous NO and ATP dose-dependently inhibited contractile activity and relaxed muscle strips with a concentration yielding a 50% effect (ED50) of 4.5 ± 2.9 × 10−6M and 3.3 ± 1.3 × 10−4M, respectively. EFS resulted in relaxation of precontracted muscle strips in all groups. When compared with controls, relaxation was decreased but not abolished byl -NAME (−0.12 ± 0.03 vs −0.33 ± 0.05, −0.07 ± 0.03 vs −0.34 ± 0.05, and 0.04 ± 0.03 vs −0.30 ± 0.04 at 2, 5, and 10 Hz, respectively,P< 0.011).d -NAME (inactive stereoisomer ofl -NAME), 4-Cl-d -Phe6Leu17-VIP, suramin, and apamin did not alter EFS-induced relaxation.ConclusionsInhibition of NO synthesis byl -NAME reduced the inhibitory response to EFS, whereas blocking ATP and VIP receptors or other effector pathways had no effect. Our findings indicate that although NO plays a predominant role in inhibitory neurotransmission in human jejunal circular muscle, another neurotransmitter(s) appears to be involved as well. These data may impact on understanding mechanisms of disorders of gut dysmotility.