Actions of the CI‐ channel blocker NPPB on absorptive and secretory transport processes of Na+ and CI‐ in rat descending colon

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Abstract
The effects of the Cl- channel blocker, NPPB (5-nitro-2-(3-phenylpropylamino)-benzoate), on the transport of Na+ and Cl- in the descending colon of the rat were studied in the Ussing chamber. In control tissue, NPPB administered at the mucosal side of the epithelium increased the short-circuit current (Isc) and inhibited the unidirectional mucosa-to-serosa fluxes of Na+ and Cl-. In HCO3-- or Cl-free media or in the presence of SITS (4-acetamido-4''-isothiocyanato-stilbene-2,2''-disulphonic acid), this increase in Isc caused by mucosal NPPB was not observed. The serosal administration of NPPB was without effect. Mucosal NPPB (10-4 mol l-1) decreased the forskolin-induced increase in Isc by only about 60%. However, the activation of the serosa-to-mucosa flux of Cl- caused by forskolin was inhibited completely. NPPB decreased the mucosa-to-serosa fluxes of Na+ and Cl- reduced additionally by forskolin. Serosal NPPB decreased Isc and Jsmsm, but had no effect on JmsNa or JmsCl. In HCO3--free buffer the increase in Isc induced by forskolin was inhibited completely by NPPB. The inhibition of Cl- secretion by NPPB fits well with the capacity of the drug to block Cl-channels. For the inhibition of neutral NaCl absorption two sites of action are discussed: an interaction with the Cl-/HCO3- exchanger or an interference with the extrusion of Cl- through the basolateral membrane.

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