title: Early nongenomic events in aldosterone action in renal collecting duct cells: PKCalpha activation, mineralocorticoid receptor phosphorylation, and cross-talk with the genomic response.
abstract: Effects of aldosterone on its target cells have long been considered to be mediated exclusively through the genomic pathway; however, evidence has been provided for rapid effects of the hormone that may involve nongenomic mechanisms. Whether an interaction exists between these two signaling pathways is not yet established. In this study, the authors show that aldosterone triggers both early nongenomic and late genomic increase in sodium transport in the RCCD(2) rat cortical collecting duct cell line. In these cells, the early (up to 2.5 h) aldosterone-induced increase in short-circuit current (Isc) is not blocked by the mineralocorticoid receptor (MR) antagonist RU26752, it does not require mRNA or protein synthesis, and it involves the PKCalpha signaling pathway. In addition, this early response is reproduced by aldosterone-BSA, which acts at the cell surface and presumably does not enter the cells (aldo-BSA is unable to trigger the late response). The authors also show that MR is rapidly phosphorylated on serine and threonine residues by aldosterone or aldosterone-BSA. In contrast, the late (4 to 24 h) aldosterone-induced increase in ion transport occurs through activation of the MR and requires mRNA and protein synthesis. Interestingly, nongenomic and genomic aldosterone actions appear to be interdependent. Blocking the PKCalpha pathway results in the inhibition of the late genomic response to aldosterone, as demonstrated by the suppression of aldosterone-induced increase in MR transactivation activity, alpha1 Na(+)/K(+)/ATPase mRNA, and Isc. These data suggest cross-talk between the nongenomic and genomic responses to aldosterone in renal cells and suggest that the aldosterone-MR mediated increase in mRNA/protein synthesis and ion transport depends, at least in part, upon PKCalpha activation. E-mail: marcel.blot-chabaud@pharmacie.univ-mrs.fr
authors.affiliation: INSERM U478, Institut Claude Bernard Physiologie et Pathologie, Faculté de Médecine Xavier Bichat, Paris, France. moellic@bichat.inserm.fr
authors.forename: Cathy
authors.initials: C
authors.lastname: Le Moëllic
authors.forename: Antoine
authors.initials: A
authors.lastname: Ouvrard-Pascaud
authors.forename: Claudia
authors.initials: C
authors.lastname: Capurro
authors.forename: Francoise
authors.initials: F
authors.lastname: Cluzeaud
authors.forename: Michel
authors.initials: M
authors.lastname: Fay
authors.forename: Frederic
authors.initials: F
authors.lastname: Jaisser
authors.forename: Nicolette
authors.initials: N
authors.lastname: Farman
authors.forename: Marcel
authors.initials: M
authors.lastname: Blot-Chabaud
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D007685:Kidney Tubules, Collecting / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000451:Mineralocorticoid Receptor Antagonists; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051381:Rats; D020239:Receptor Cross-Talk / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D012710:Serum Albumin, Bovine; D013148:Spironolactone; D000450:Aldosterone; C047175:7-propyl spirolactone; D012964:Sodium; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D000254:Sodium-Potassium-Exchanging ATPase