CFTR disruption impairs cAMP-dependent Cl- secretion in primary cultures of mouse cortical collecting ducts

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in the renal cortical collecting duct (CCD) has not yet been fully elucidat ed. Here, we investigated the effects of deamino-8-D-arginine vasopressin ( dDAVP) and isoproterenol (ISO) on NaCl transport in primary cultured CCDs m icrodissected from normal [CFTR(+/+)] and CFTR-knockout [CFTR(-/-)] mice. d DAVP stimulated the benzamyl amiloride (BAm)-sensitive transport of Na+ ass essed by the short-circuit current (I-sc) method in both CFTR(+/+) and CFTR (-/-) CCDs to a very similar degree. Apical addition of 5-nitro-2-(3-phenyl propylamino)-benzoate (NPPB) or glibenclamide partially inhibited the rise in I-sc induced by dDAVP and ISO in BAm-treated CFTR(+/+) CCDs, whereas dDA VP, ISO, and NPPB did not alter I-sc in BAm-treated CFTR(-/-) CCDs. dDAVP s timulated the apical-to-basal flux and, to a lesser extent, the basal-to-ap ical flux Of Cl-36(-) in CFTR(+/+) CCDs. dDAVP also increased the apical-to -basal Cl-36(-) flux in CFTR(-/-) CCDs but not the basal-to-apical Cl-36(-) flux. These results demonstrate that CFTR mediates the cAMP-stimulated com ponent of secreted Cl- in mouse CCD.