Interaction of NO and VIP in gastrointestinal smooth muscle relaxation.
Interaction of NO and VIP in gastrointestinal smooth muscle relaxation.
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DOI：
10.2174/1381612043383890
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发表时间：
2004-07
影响因子：
3.1
通讯作者：
L. V. Geldre;Romain Lefebvre
中科院分区：
文献类型：
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作者：
L. V. Geldre;Romain Lefebvre
胃肠道（GI）平滑肌细胞的活动是由位于环形肌层和纵向肌层之间的肌丛中的收缩性胆碱能神经元和松弛性非肾上腺素能非胆碱能神经元控制的。NANC松弛的减少或增加可能参与功能性GI运动障碍的病理生理。血管活性肠多肽（VIP）和一氧化氮（NO）是主要的抑制性NANC神经递质。作为经典的神经递质，VIP储存在神经末梢的囊泡中，而NO则由NO合成酶（nNOS）的神经元异构体根据需要合成。不同物种胃肠道不同区域的VIP/nNOS在肌肠神经元中共定位，表明VIP和NO是共递质。在突触前水平，VIP和NO可以相互诱导释放。这一机制最明确的证据是在离体肌肠神经节中获得的，VIP诱导NO释放，NO促进VIP释放。在突触后水平，许多研究支持VIP和NO是平行的共递质，分别通过腺苷酸环化酶/3‘5’环磷酸腺苷（cAMP）和鸟苷酸环化酶/3‘5’环磷酸鸟苷途径起作用。主要基于在离体GI平滑肌细胞中获得的结果，提出了一系列突触后VIP/NO相互作用模型，其中VIP是主要的神经递质，部分通过VPAC受体和腺苷酸环化酶/cAMP途径起作用，但也通过诱导肌肉NO的产生。最近的研究结果表明，VIP从离体平滑肌细胞中释放NO的能力与分离过程中细胞中诱导NOS （inducible NOS, iNOS）的产生有关。NO和VIP对GI NANC松弛的相对贡献随组织和神经放电频率的不同而不同，因此干扰其中任何一种都会导致不同的效果。
Gastrointestinal (GI) smooth muscle cell activity is controlled by contractile cholinergic neurons and relaxant non-adrenergic non-cholinergic (NANC) neurons in the myenteric plexus between the circular and longitudinal muscle layer. Decreased or increased NANC relaxation might be involved in the pathophysiology of functional GI motility disorders. Vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) are the primary inhibitory NANC neurotransmitters. As classic neurotransmitters, VIP is stored in vesicles in the nerve endings, while NO is synthetized on demand by the neuronal isoform of NO synthase (nNOS). The VIP/nNOS co-localization in myenteric neurons, reported for various regions of the GI tract in different species, suggests that VIP and NO are co-transmitters. At the presynaptic level, VIP and NO can induce each others release. Most clear-cut evidence for this mechanism was obtained in isolated myenteric ganglia where VIP induced NO release, and NO facilitated VIP release. At the postsynaptic level, many studies support that VIP and NO are parallel co-transmitters, acting via the adenylate cyclase/3'5' adenosine cyclic monophosphate (cAMP) and guanylate cyclase/3'5' cyclic guanosine monophosphate pathway respectively. Mainly based on results obtained in isolated GI smooth muscle cells, a serial postsynaptic VIP/NO interaction model was proposed, whereby VIP is the principle neurotransmitter, acting partially via a VPAC receptor and the adenylate cyclase/cAMP pathway but also by induction of muscular NO production. Recent results suggest that the capacity of VIP to release NO from isolated smooth muscle cells is related to the induction of inducible NOS (iNOS) in the cells during the isolation procedure. The relative contribution of NO and VIP to GI NANC relaxation differs upon tissue and nerve firing frequency, so that interference with either of them will lead to varying effects.