The mechanism by which excess quantities of bile salts in the colon produce diarrhea is not known. Therefore, experiments were performed in which the effect of conjugated dihydroxy bile salts on ion transport was evaluated in the in vitro short-circuited rat colon. 2 mM glycochenodeoxycholic acid (GCDC), taurochenodeoxycholic acid (TCDC), or taurodeoxycholic acid caused a prompt increase in short-circuit current (Isc) and electrical potential difference (PD). Similar results were obtained when theophylline was added. Removal of HCO2 and C1 prevented the effects of both bile salts and theophylline. Pretreatment with theophylline blocked the increase in Isc and PD produced by TCDC and pretreatment with either TCDC or GCDC inhibited the expected theophylline response. Na fluxes in the presence of both TCDC and theophylline demonstrated a decrease in net absorption; and TCDC decreased net C1 absorption and theophylline caused a reversal of net C1 absorption to net C1 secretion. It is proposed that the diarrhea associated with cholerheic enteropathy is produced by active anion secretion possibly mediated by cyclic AMP.
Henry J. Binder, Claudia L. Rawlins