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

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 for 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 FNasm, but had no effect on FNams or FClmas. 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.