Acta Physiol Scand zyxwvutsrqp 1994, zyxwvuts 151, 45-50 Effect of NPPB on chloride (CI-) transport in distal colon of potassium (K+) adapted rats D. VERON,' R. S. MARTIN,' E. ESCOBAR,' D. TUFARO,' P. VISCONTI,2 J. G. TEZON' and E. E. ARRIZURIETA' zyxwvu ' Instituto de Investigaciones MCdicas Alfredo Lanari, University of Buenos Aires, and ' Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires, Argentina VERON, D., MARTIN, R.S., ESCOBAR, E., TUFARO, D., VISCONTI, P., TEZON, J.G. & ARRIZURIETA, E.E. 1994. Effect of NPPB on chloride (Cl-) transport in distal colon of potassium (K') adapted rats. zyxwv Acta Physiol Scand 151, 45-50. Received 18 January 1993, accepted 19 November 1993. ISSN 0001-6772. Instituto de Investigaciones Medicas Alfredo Lanari, University of Buenos Aires, and Instituto de Biologia y Medicina Experimental, CONICET, Argentina. Secondary hyperaldosteronism enhances the rate of K secretion in distal colon, at least in part, through the stimulation of Na+-K+-CI- cotransport across the basolateral membrane. To maintain a constant intracellular C1- activity an increase in C1- transport out of the cell must be assumed. We explored, under amiloride lo-' M and short circuited conditions, conductive pathways for C1- exit in the distal colon of K+-adapted rats by means of a putative C1- channel blocker, NPPB (5-nitro-2(3-phenyl- propylamino-benzoate. Results prior to NPPB showed an increase in J C P after zy K+ loading from 5.84 zyxwvu f 0.66 to 8.33 f0.86 and JClsm from 4.77 f 0.55 to 8.16 f 0.96 pEq h-' cm12 (P < 0.001), when compared with controls. Net fluxes were not different between groups. Luminal NPPB in K+ adaptation resulted in a decrease of JCP", from 7.85 -t 1.5 to 6.69 f 1.5 pEq h-' cm-' (P < 0.05). There were no changes in both unidirectional CI- fluxes in controls under luminal NPPB and in potential difference (V) and short-circuit current ( zyxwvu Isc) under any condition. Finally, K' adaptation resulted in an increase of luminal cyclic AMP (CAMP) concentration (0.09k0.02 to 0.20 f 0.03 pmol 100 PI-', P < 0.05), when compared with control rats. The data may suggest a transcellular recycling of CI- and an activated NPPB inhibitable serosal to mucosal CI- pathway on luminal membrane in the K+ adapted state, possibly mediated by an increase in CAMP production. Key words: Amiloride. chloride, distal colon, NPPB, potassium adaptation, rat, rubidium. Chronic K+ loading enhances the rate of K+ secretion through transport changes in both apical and basolateral cell membranes. Among these, aldosterone-induced K t secretion in rat distal colon is associated with the emergence of an electrogenic Nat absorption and the stimu- lation of Na+-K+ pump by mediating the uptake of Kt across the basolateral membrane (Hayslett & Binder 1982). In a second step, Kt ions diffuse from cell to lumen along a favourable elec- Correspondence: Rodolfo S. Martin, Instituto de Investigaciones Medicas Alfredo Lanari, Donato Alvarez 3150, 1427 Buenos Aires, Argentina. trochemical gradient and, at least in part, through an enhanced Kt-conductive pathway in the apical membrane (Siga el al. 1989). In contrast to the classical Na+ absorption- dependent mode, K+ secretion has been recently associated with C1- movements (McCabe et al. 1985). In this regard, Sweiry & Binder (1989) have recently found an enhancement of Nat-K+- C1- cotransport across the basolateral membrane of distal colon in a model of secondary hyper- aldosteronism after Na+ depletion. If a major source of K+ for secretion is that which enters the cell via the Na+-K+-Cl- cotransport process (Sweiry & Binder 1989), 45