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血管活性肠肽释放的接头前抑制

Prejunctional inhibition of vasoactive intestinal peptide release.

作者信息

Grider J R, Makhlouf G M

出版信息

Am J Physiol. 1987 Jul;253(1 Pt 1):G7-12. doi: 10.1152/ajpgi.1987.253.1.G7.

DOI:10.1152/ajpgi.1987.253.1.G7
PMID:3605338
Abstract

The role of vasoactive intestinal peptide (VIP) and its homologue, peptide histidine isoleucine (PHI), as neurotransmitters of inhibitory motor nerves of the gut, were examined in strips of guinea pig taenia coli and gastric fundic muscle. The stoichiometry of VIP release and muscle relaxation was determined in the presence and absence of the bee venom peptide, apamin, and the existence of prejunctional VIP/PHI receptors capable of regulating VIP/PHI release was explored. In both types of muscle, relaxation induced by field stimulation was proportional to the amount of VIP released. Apamin inhibited relaxation and VIP release in a dose-dependent manner: maximal relaxation was inhibited by 85-96% at 10(-7)-10(-6) M apamin. Analysis of residual responses showed that apamin did not affect the stoichiometry of VIP release and muscle relaxation. Because apamin had no effect on basal tone or on relaxation induced by exogenous VIP, its effect on neurally induced relaxation was attributed to inhibition of VIP release. Both secretin and PHI inhibited neurally induced VIP release in the two types of muscle. At the optimal concentration of 10(-7) M, secretin inhibited VIP release by 52%, whereas the closer neural homologue, PHI, abolished VIP release. The dose-dependent inhibition of VIP release by PHI, which is cosynthesized and coreleased with VIP, indicates the existence of prejunctional inhibitory VIP/PHI autoreceptors capable of regulating VIP/PHI release.

摘要

在豚鼠结肠带和胃底肌条中,研究了血管活性肠肽(VIP)及其同系物肽组氨酸异亮氨酸(PHI)作为肠道抑制性运动神经递质的作用。在存在和不存在蜂毒肽阿帕明的情况下,测定了VIP释放与肌肉松弛的化学计量关系,并探讨了能够调节VIP/PHI释放的突触前VIP/PHI受体的存在情况。在这两种类型的肌肉中,场刺激诱导的松弛与VIP释放量成正比。阿帕明以剂量依赖的方式抑制松弛和VIP释放:在10^(-7)-10^(-6) M阿帕明浓度下,最大松弛被抑制85%-96%。对残余反应的分析表明,阿帕明不影响VIP释放与肌肉松弛的化学计量关系。由于阿帕明对外源性VIP诱导的基础张力或松弛没有影响,其对神经诱导的松弛的作用归因于对VIP释放的抑制。促胰液素和PHI均抑制这两种类型肌肉中神经诱导的VIP释放。在最佳浓度10^(-7) M时,促胰液素抑制VIP释放52%,而更接近的神经同系物PHI则完全消除VIP释放。与VIP共同合成和共同释放的PHI对VIP释放的剂量依赖性抑制表明存在能够调节VIP/PHI释放的突触前抑制性VIP/PHI自身受体。

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Neurogastroenterol Motil. 2009 Jul;21(7):754-e47. doi: 10.1111/j.1365-2982.2009.01271.x. Epub 2009 Feb 23.
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Alterations to enteric neural signaling underlie secretory abnormalities of the ileum in experimental colitis in the guinea pig.豚鼠实验性结肠炎中,肠道神经信号的改变是回肠分泌异常的基础。
Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G717-26. doi: 10.1152/ajpgi.90472.2008. Epub 2009 Feb 12.
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Gene therapy of Cav1.2 channel with VIP and VIP receptor agonists and antagonists: a novel approach to designing promotility and antimotility agents.
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Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G187-G196. doi: 10.1152/ajpgi.00047.2008. Epub 2008 May 8.
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Br J Pharmacol. 2001 Jan;132(2):507-17. doi: 10.1038/sj.bjp.0703814.
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Br J Pharmacol. 1999 Apr;126(7):1543-52. doi: 10.1038/sj.bjp.0702450.
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