EFFECT OF NPPB ON CHLORIDE (CL-) TRANSPORT IN DISTAL COLON OF POTASSIUM (K+) ADAPTED RATS

Secondary hyperaldosteronism enhances the rate of K secretion in dista l colon, at least in part, through the stimulation of Na+-K+-Cl- cotra nsport across the basolateral membrane. To maintain a constant intrace llular Cl- activity an increase in Cl- transport out of the cell must be assumed. We explored, under amiloride 10(-4) M and short circuited conditions, conductive pathways for Cl- exit in the distal colon of K-adapted rats by means of a putative Cl- channel blocker, NPPB (5-nitr o-2(3-phenylpropylamino-benzoate. Results prior to NPPB showed an incr ease in JCl(ms) after K+ loading from 5.84+/-0.66 to 8.33+/-0.86 and J Cl(sm) from 4.77+/-0.55 to 8.16+/-0.96 mu Eq h(-1) cm(-2) (P < 0.001), when compared with controls. Net fluxes mere not different between gr oups. Luminal NPPB in K+ adaptation resulted in a decrease of JCl(sm), from 7.85+/-1.5 to 6.69+/-1.5 mu Eq h(-1) cm(-2) (P < 0.05). There we re no changes in both unidirectional Cl- fluxes in controls under lumi nal NPPB and in potential difference (V) and short-circuit current (I- sc) under any condition. Finally, K+ adaptation resulted in an increas e of luminal cyclic AMP (cAMP) concentration (0.09+/-0.02 to 0.20+/-0. 03 pmol 100 mu l(-1), P < 0.05), when compared with control rats. The data may suggest a transcellular recycling of Cl- and an activated NPP B inhibitable serosal to mucosal Cl- pathway on luminal membrane in th e K+ adapted state, possibly mediated by an increase in cAMP productio n.