Influence of dietary sodium on the renal isoforms of 11 beta-hydroxysteroid dehydrogenase.
Endogenous glucocorticoids are converted to their biologically inert 11-dehydroderivatives by isoforms of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). The low-K(m), NAD(+)-dependent renal isoform (Type 2) identified in the distal nephron protects mineralocorticoid receptors from activation by endogenous glucocorticoids. The function of high-K(m), NADP(+)-dependent renal isoform (Type 1) is less well understood. Since glucocorticoids may modulate sodium transport in renal proximal tubules (PT), we hypothesized that Type 1 activity in this segment may be regulated by dietary Na(+)-11 beta-HSD activity was assessed in homogenates of canine PT by the conversion of cortisol to cortisone in the presence of NADP+ 200 microM. A high-Na+ diet for 4 days increased the Vmax 4-fold, with no change in the Type 1 K(m) (40 mEq/day Na+ diet: K(m) 0.959 microM, Vmax 3.40 pmoles/min/mg protein versus 150 mEq/day Na+ diet: K(m) 0.962 microM, Vmax 14.8 pmoles/min/mg protein). Type 1 mRNA also rose in the salt repleted animals. The high-Na+ diet produced no detectable change in the Type 2 isoform enzyme kinetics and mRNA level. No reverse oxo-reductase activity was noted with either renal isoform. Thus, renal Type 1 11 beta-HSD can be regulated by dietary Na+ independent of changes in the renal Type 2 isoform.
Brem
A S
AS
Division of Pediatric Nephrology, Brown University, Providence, Rhode Island 0290, USA.
Bina
R B
RB
King
T
T
Chobanian
M C
MC
Morris
D J
DJ
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D004285:Dogs; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007672:Kidney Cortex / Q000737:chemistry / Q000201:enzymology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D009243:NAD; D009249:NADP / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
D007527:Isoenzymes; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D009243:NAD; D009249:NADP; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases