title: Regulation of prostasin by aldosterone in the kidney.
abstract: 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.
authors.affiliation: Third Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Narikiyo
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kitamura
authors.forename: Masataka
authors.initials: M
authors.lastname: Adachi
authors.forename: Taku
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Kozo
authors.initials: K
authors.lastname: Iwashita
authors.forename: Naoki
authors.initials: N
authors.lastname: Shiraishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonoguchi
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Chen
authors.forename: Karl X
authors.initials: KX
authors.lastname: Chai
authors.forename: Julie
authors.initials: J
authors.lastname: Chao
authors.forename: Kimio
authors.initials: K
authors.lastname: Tomita
mesh_terms: 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
chemical_list: D000450:Aldosterone; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D015222:Sodium Channels; D000099271:Prostasin