Dihydroxy bile salt-induced alterations in NaCl transport across the rabbit colon

Abstract

The effects of increasing mucosal or serosal concentrations (1–4 mM) of taurochenodeoxycholate (TCDC) on sodium chloride transport across the isolated, short-circuited rabbit colon were examined. Mucosal TCDC produced dose-related increases in tissue conductance (Gt) and the unidirectional fluxes of Na+ and Cl- and dose-related decreases in net NaCl absorption. At 4 mM mucosal TCDC, Gt was increased fivefold, net sodium flux (JNanet) was reduced 50%, and JClnet was abolished. Serosal TCDC also produced dose-dependent changes in permeability that were quantitatively different. Four millimolar serosal TCDC produced a 2.7-fold increase in Gt, abolished JNanet, and stimulated electrogenic Cl- secretion. TCDC-induced Cl- secretion was stimulated by 10(-5) M serosal TCDC, inhibited by serosal furosemide or ouabain, did not alter theophylline-induced secretion (and vice versa), and occurred in the absence of serosal Ca2+. It is suggested that 1) TCDC inhibition of sodium absorption is indirect (i.e., not simply due to a reduction in the activity of the Na “pump,” since Cl- secretion persists during conditions that abolish JNanet) and 2) TCDC induces Cl- secretion by enhancing the activity of basolateral membrane adenylate cyclase.