Calcium channels and intestinal fluid secretion: an experimental study in vivo in rats

Several mechanisms involved in nervous secretory reflex(es) of the enteric nervous system may be dependent on the flux of calcium across the plasma membrane, which may be controlled by voltage-gated calcium channels. In this study, we investigated the importance of plasma membrane calcium channels for intestinal fluid secretion. Two types of studies were performed, in which intestinal net fluid transport in anaesthetized rats was followed with a gravimetric method. First, the effects on intestinal fluid transport of placing A23187, a calcium ionophore, in the intestinal lumen was studied. A23187 induced in a dose-dependent manner a net fluid secretion, which was abolished by giving hexamethonium (10 mg kg(-1) body wt) i.v. or placing lidocaine (1% solution) on the intestinal serosa. Nifedipine (5.75 micromol kg(-1) body wt i.v.) also abolished the fluid secretion caused by the ionophore. In the second study, the effects of various calcium channel blockers (gadolinium chloride, nifedipine, verapamil) were tested on the cholera toxin-induced secretion. It was attenuated by luminal application of gadolinium chloride (1-10 mM) or nifedipine (10-200 microM). Intravenously administered nifedipine (2.5-5.75 micromol kg(-1) body wt) abolished cholera toxin-evoked secretion dose-dependently, whereas verapamil (0.05-1 micromol kg(-1) body wt) was without consistent effect. It is concluded that the fluid secretion evoked by placing A23187 in the intestinal lumen in vivo was induced via an activation of the enteric nervous system. Cholera secretion was attenuated or abolished by calcium channel blockers of the L- or N-type.