Glucocorticoid stimulation of Na-K-ATPase in superfused distal segments of kidney tubules in vitro.
The ability of glucocorticoids to regulate Na-K-ATPase activity directly was assessed in separated rat kidney tubules derived from the distal nephron. These tubules were superfused under sterile conditions and maintained in a viable condition for at least 24 h in a newly devised apparatus. Viability was assessed by measuring O2 consumption, protein/DNA ratios, and Na-K-ATPase and Mg-ATPase activities. At a concentration of 10(-8) M, dexamethasone elicited a 27% increase in tubular Na-K-ATPase activity in 6 h and a 32% increase in 24 h. In a separate series, assayed at 24 h, the maximal effect was obtained at a dexamethasone concentration of less than 10(-8) M, and by inspection half-maximal stimulation was obtained at approximately 10(-9) M. At a concentration of 10(-7) M, 17 beta-estradiol, testosterone, progesterone, and deoxycorticosterone acetate had no significant effect on tubular Na-K-ATPase activity. These results as well as the time-course and dose-response data imply that the response is mediated by the glucocorticoid receptor pathway. Since the magnitude of response in vitro was similar to the one obtained after injection of dexamethasone in vivo, much if not all of the action appears to be direct and independent of glucocorticoid-induced changes in the filtered Na+ load.
D000315:Adrenalectomy; D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology*; D003907:Dexamethasone / Q000097:blood / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D006651:Histocytochemistry; D007684:Kidney Tubules / Q000201:enzymology*; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology
D013739:Testosterone; D003900:Desoxycorticosterone; D004958:Estradiol; D003907:Dexamethasone; D000254:Sodium-Potassium-Exchanging ATPase