INTERRELATIONSHIP BETWEEN THE NA+ GLUCOSE COTRANSPORTER AND CFTR IN CACO-2 CELLS - RELEVANCE TO CYSTIC-FIBROSIS/

Both the Na+-dependent glucose cotransporter (SGLT1) and the cystic fi brosis transmembrane conductance regulator (CFTR) modulate Na+ and flu id movement, although in opposite directions. Yet few studies have inv estigated a possible interrelationship between these two transporters. By using the Caco-2 human colon carcinoma cell line, we confirmed tha t the activities of these transporters increased with spontaneous diff erentiation to the enterocytic phenotype. We showed that SGLT1 was pos itively regulated by Cl- and that optimal activity of CFTR was depende nt on the presence of glucose. We also demonstrated that inhibition of CFTR by glibenclamide or diphenylamine-2-carboxylate did not modify t he activity of SGLT1 and inhibition of SGLT1 by phlorizin did not modi fy the activity of CFTR, although it resulted in inhibition of glycoco njugate synthesis. These results point to positive substrate-cross reg ulation of SGLT1 and CFTR and suggest that NaCl and glucose are import ant for not only Na+ absorption and fluid movement, but also for cAMP- dependent Cl- efflux, and glycoconjugate synthesis, functions that are known to be anomalous in cystic fibrosis. (C) J. Cell. Physiol. 176:4 72-481, 1998. (C) 1998 Wiley-Liss, Inc.