Regulation of prostasin by aldosterone in the kidney.
Prostasin is a serine protease present in mammalian urine that increases the activity of the epithelial sodium channel (ENaC) when the two are coexpressed in Xenopus oocytes. To determine if aldosterone, one of the principal regulators of urinary Na reabsorption by the distal nephron, affects prostasin expression, we examined prostasin mRNA and protein in a cultured mouse cortical collecting duct cell line (M-1), whole rats, and patients with primary aldosteronism. Aldosterone treatment of M-1 cells substantially increased prostasin expression and stimulated (22)Na uptake. Urinary excretion of prostasin in rats that were infused with aldosterone likewise increased by approximately 4-fold when compared with the vehicle-infused rats. Finally, urinary excretion of prostasin in patients with primary aldosteronism was substantially increased when compared with normal patients. Adrenalectomy reduced urinary prostasin excretion to control levels, whereas urinary prostasin levels were not altered in patients undergoing surgery for other reasons. In patients with primary aldosteronism, reduction in the urinary excretion of prostasin correlated with the increase in the urinary Na/K ratio. These findings, together with our previous report that prostasin activates the amiloride-sensitive Na currents through ENaC, demonstrate that prostasin regulates Na balance in vivo by virtue of its heightened expression in the presence of aldosterone.
Narikiyo
Takefumi
T
Third Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan.
Kitamura
Kenichiro
K
Adachi
Masataka
M
Miyoshi
Taku
T
Iwashita
Kozo
K
Shiraishi
Naoki
N
Nonoguchi
Hiroshi
H
Chen
Li-Mei
LM
Chai
Karl X
KX
Chao
Julie
J
Tomita
Kimio
K
D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D053503:Epithelial Sodium Channels; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery; D007668:Kidney / Q000502:physiology*; D007700:Kinetics; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000235:genetics* / Q000502:physiology* / Q000652:urine; D015222:Sodium Channels / Q000378:metabolism; D000099271:Prostasin
D000450:Aldosterone; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D015222:Sodium Channels; D000099271:Prostasin