Differential effects of aldosterone and vasopressin on chloride fluxes in transimmortalized mouse cortical collecting duct cells.
The effects of aldosterone and vasopressin on Cl- transport were investigated in a mouse cortical collecting duct (mpkCCD) cell line derived from a transgenic mouse carrying the SV40 large T antigen driven by the proximal regulatory sequences of the L-pyruvate kinase gene. The cells had features of a tight epithelium and expressed the amiloride-sensitive sodium channel and the cystic fibrosis transmembrane conductance regulator (CFTR) genes. dD-arginine vasopressin (dDAVP) caused a rapid, dose-dependent, increase in short-circuit current (Isc). Experiments with ion channel blockers and apical ion substitution showed that the current represented amiloride-sensitive Na+ and 5-nitro-2-(3-phenylpropylamino)benzoate-sensitive and glibenclamide-sensitive Cl- fluxes. Aldosterone (5 x 10(-7)M for 3 or 24 hr) stimulated Isc and apical-to-basal 22Na+ flux by 3-fold. 36Cl- flux studies showed that dDAVP and aldosterone stimulated net Cl- reabsorption and that dDAVP potentiated the action of aldosterone on Cl- transport. Whereas aldosterone affected only the apical-to-basal 36Cl- flux, dDAVP mainly increased the apical-to-basal Cl- flux and the basal-to-apical flux of Cl- to a lesser extent. These results suggest that the discrete dDAVP-elicited Cl- secretion involves the CFTR and that dDAVP and aldosterone may affect in different ways the observed increased Cl- reabsorption in this model of mouse cultured cortical collecting duct cells.
Duong Van Huyen
J
J
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 478, Institut Fédératif de Recherche 02, Faculté de Médecine Xavier Bichat, B.P. 416, 75870 Paris Cédex 18, France.
Bens
M
M
Vandewalle
A
A
D000450:Aldosterone / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002461:Cell Line, Transformed; D018118:Chloride Channels / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D053503:Epithelial Sodium Channels; D015870:Gene Expression; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009579:Nitrobenzoates / Q000494:pharmacology; D015222:Sodium Channels / Q000096:biosynthesis / Q000378:metabolism; D012979:Sodium Radioisotopes; D014667:Vasopressins / Q000494:pharmacology*
D018118:Chloride Channels; D053503:Epithelial Sodium Channels; D009579:Nitrobenzoates; D015222:Sodium Channels; D012979:Sodium Radioisotopes; D014667:Vasopressins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D000450:Aldosterone; D000584:Amiloride; D003894:Deamino Arginine Vasopressin