The early non-genomic aldosterone-induced increase in sodium transport is a membrane-initiated event that requires protein carboxyl methylation in renal cells.
Effects of aldosterone on its target cells are generally considered to be mediated through the genomic pathway. However, recent studies have evidenced rapid effects of the hormone that involve a non-genomic mechanism. In this study, we show that, in the RCCD2 rat cortical collecting duct cell line, the early effect of the hormone on transepithelial sodium transport is neither antagonized by the mineralo- and glucocorticoid receptors antagonists RU26752 and RU486, nor blocked by mRNA and protein synthesis inhibitors. Interestingly, the plasma membranes of RCCD2 cells specifically bind 3H-aldosterone but not 3H-dexamethasone, a binding that is not displaced in the presence of RU26752 or RU486, suggesting the presence of an aldosterone membrane receptor. In addition, the early aldosterone-induced increase in sodium transport is blocked by the addition of a specific inhibitor of carboxyl methyl transferase. These results suggest that, in RCCD2 cells, the early aldosterone-induced increase in sodium transport is not mediated through the genomic pathway but through a membrane receptor-mediated signal and could involve a rapid carboxyl methylation process regulated by aldosterone.
Le Moëllic
C
C
INSERM U478, Institut Claude Bernard "Physiologie et Pathologie", Faculté de Médecine Xavier Bichat, B.P. 416, 75870 Paris 18, France.
Cluzeaud
F
F
Fay
M
M
Blot-Chabaud
M
M
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D046508:Culture Techniques; D053503:Epithelial Sodium Channels; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008745:Methylation / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D053503:Epithelial Sodium Channels; D011506:Proteins; D012333:RNA, Messenger; C440894:Scnn1a protein, rat; D015222:Sodium Channels; D014316:Tritium; D000450:Aldosterone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase