title: CFTR disruption impairs cAMP-dependent Cl(-) secretion in primary cultures of mouse cortical collecting ducts.
abstract: The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in the renal cortical collecting duct (CCD) has not yet been fully elucidated. Here, we investigated the effects of deamino-8-D-arginine vasopressin (dDAVP) and isoproterenol (ISO) on NaCl transport in primary cultured CCDs microdissected from normal [CFTR(+/+)] and CFTR-knockout [CFTR(-/-)] mice. dDAVP stimulated the benzamyl amiloride (BAm)-sensitive transport of Na(+) assessed 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-phenylpropylamino)-benzoate (NPPB) or glibenclamide partially inhibited the rise in I(sc) induced by dDAVP and ISO in BAm-treated CFTR(+/+) CCDs, whereas dDAVP, ISO, and NPPB did not alter I(sc) in BAm-treated CFTR(-/-) CCDs. dDAVP stimulated the apical-to-basal flux and, to a lesser extent, the basal-to-apical flux of (36)Cl(-) in CFTR(+/+) CCDs. dDAVP also increased the apical-to-basal (36)Cl(-) flux in CFTR(-/-) CCDs but not the basal-to-apical (36)Cl(-) flux. These results demonstrate that CFTR mediates the cAMP-stimulated component of secreted Cl(-) in mouse CCD.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 478, Faculté de Médecine Xavier Bichat, 75870 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Bens
authors.forename: J P
authors.initials: JP
authors.lastname: Duong Van Huyen
authors.forename: F
authors.initials: F
authors.lastname: Cluzeaud
authors.forename: J
authors.initials: J
authors.lastname: Teulon
authors.forename: A
authors.initials: A
authors.lastname: Vandewalle
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D002712:Chlorides / Q000378:metabolism*; D003433:Crosses, Genetic; D000242:Cyclic AMP / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D053503:Epithelial Sodium Channels; D005905:Glyburide / Q000494:pharmacology; D006720:Homozygote; D007545:Isoproterenol / Q000494:pharmacology; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009579:Nitrobenzoates / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000235:genetics; D012965:Sodium Chloride / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D053503:Epithelial Sodium Channels; D009579:Nitrobenzoates; D012333:RNA, Messenger; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C013407:benzamil; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D012965:Sodium Chloride; D000584:Amiloride; D000242:Cyclic AMP; D003894:Deamino Arginine Vasopressin; D007545:Isoproterenol; D005905:Glyburide