传入神经末梢在缓激肽刺激大鼠离体结肠离子转运中的作用。

The involvement of afferent nerve terminals in the stimulation of ion transport by bradykinin in rat isolated colon.

作者信息

Perkins M N, Forster P L, Dray A

机构信息

Sandoz Institute for Medical Research, London.

出版信息

Br J Pharmacol. 1988 May;94(1):47-54. doi: 10.1111/j.1476-5381.1988.tb11498.x.

DOI:10.1111/j.1476-5381.1988.tb11498.x

PMID:3401643

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1853918/

Abstract

The actions of bradykinin (Bk) were investigated on rat colon epithelium preparations that had been stripped of the muscle layers. The electrogenic ion flux was monitored by measuring changes in the short circuit current (SCC) produced by addition of drugs. Bk, administered to the basolateral side, but not apical side, of the epithelium evoked an increase in SCC which was separable into two distinct components, both of which were mediated mainly by chloride efflux. 2. The early component was robust, reproducible and exhibited clear concentration-dependency with an EC50 of 6.2 nM. The second phase of the response exhibited a much slower time course than the first phase and diminished amplitude with repeated applications of Bk. 3. In preparations of unstripped epithelium, bradykinin (Bk) evoked mainly a slow neurogenic response which was attenuated or abolished by tetrodotoxin (TTX). When the epithelium was stripped off, TTX had little effect either on the baseline SCC or on responses to Bk. 4. Perfusion with zero calcium solution did not affect the early phase but abolished the late phase of the Bk response. Verapamil (20 microM), but not nifedipine (20 microM), also attenuated the later phase of the response. 5. Capsaicin (2 microM) administered to the basolateral, but not the apical, side produced an increase in SCC. Following desensitization to capsaicin the second phase of the response to Bk was abolished with little effect on the initial response to Bk. 6. The data suggest that Bk increases the efflux of chloride ions across the colonic epithelium in at least two ways: (a) by an action on the epithelial cells and (b) by an action on neuronal elements within the epithelium. This latter effect of Bk is due to stimulation of capsaicin-sensitive nerve terminals within the mucosa of the colon epithelium causing the release of a mediator which is responsible for the second phase of the response to Bk.

摘要

研究了缓激肽（Bk）对已去除肌肉层的大鼠结肠上皮制剂的作用。通过测量添加药物后产生的短路电流（SCC）变化来监测电生性离子通量。将Bk施用于上皮细胞的基底外侧而非顶端，可引起SCC增加，该增加可分为两个不同的成分，两者均主要由氯离子外流介导。2. 早期成分强烈、可重复，且表现出明显的浓度依赖性，半数有效浓度（EC50）为6.2 nM。反应的第二阶段比第一阶段的时间进程慢得多，且随着Bk的重复应用，幅度减小。3. 在未去除上皮的制剂中，缓激肽（Bk）主要引起缓慢的神经源性反应，该反应被河豚毒素（TTX）减弱或消除。当去除上皮时，TTX对基线SCC或对Bk的反应几乎没有影响。4. 用零钙溶液灌注不影响早期阶段，但消除了Bk反应的后期阶段。维拉帕米（20 μM）而非硝苯地平（20 μM）也减弱了反应的后期阶段。5. 将辣椒素（2 μM）施用于基底外侧而非顶端，可使SCC增加。对辣椒素脱敏后，对Bk反应的第二阶段被消除，而对Bk的初始反应影响很小。6. 数据表明，Bk至少通过两种方式增加氯离子跨结肠上皮的外流：（a）通过作用于上皮细胞；（b）通过作用于上皮内的神经元成分。Bk的后一种作用是由于刺激了结肠上皮黏膜内对辣椒素敏感的神经末梢，导致一种介质释放，该介质负责对Bk反应的第二阶段。