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 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.
Bens
M
M
Institut National de la Santé et de la Recherche Médicale, Unité 478, Faculté de Médecine Xavier Bichat, 75870 Paris, France.
Duong Van Huyen
J P
JP
Cluzeaud
F
F
Teulon
J
J
Vandewalle
A
A
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
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