DIPEPTIDE-INDUCED CL- SECRETION IN PROXIMAL TUBULE CELLS

During a survey of dipeptides that might be transported by the renal P EPT2 transporter in proximal tubule cells, we discovered that acidic d ipeptides could stimulate transient secretory anion current and conduc tance increases in intact cell monolayers. The stimulatory effect of a cidic dipeptides was observed in several proximal tubule cell lines th at have been recently developed by immortalization of early proximal t ubule primary cultures from the Wistar-Kyoto and spontaneously hyperte nsive rat strains and humans, suggesting that this phenomenon is a cha racteristic of proximal tubule cells. The electrical current induced i n intact monolayers by Ala-Asp, a representative of these acidic dipep tides, must represent Cl- secretion rather than Na+ or H+ absorption, because 1) it was Na+ independent, 2) it showed a pH dependence differ ent from that of the PEPT2 cotransporter, and 3) it correlated with an Ala-Asp-induced increase in Cl- conductance of the apical membrane in basolaterally amphotericin B-permeabilized monolayers. The secretory current could be inhibited by stilbene disulfonates, but not diphenyla mine-2-carboxylates, suggesting a non-cystic fibrosis transmembrane co nductance regulator type of Cl- conductance. The effect of Ala-Asp was dose dependent, with an apparent 50% effective concentration of simil ar to 1 mM. Ala-Asp also produced intracellular acidification, suggest ing that acidic dipeptides are also substrates for an H+-peptide cotra nsporter.