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

Abstract

1. 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.