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 prosta...

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Published in:The Journal of clinical investigation 2002-02, Vol.109 (3), p.401-408
Main Authors: Narikiyo, Takefumi, Kitamura, Kenichiro, Adachi, Masataka, Miyoshi, Taku, Iwashita, Kozo, Shiraishi, Naoki, Nonoguchi, Hiroshi, Chen, Li-Mei, Chai, Karl X, Chao, Julie, Tomita, Kimio
Format: Article
Language:English
Subjects:
Adrenalectomy
Aldosterone - pharmacology
Aldosterone - physiology
Animals
Cell Line
Epithelial Sodium Channels
Female
Gene Expression Regulation - drug effects
Humans
Hyperaldosteronism - genetics
Hyperaldosteronism - physiopathology
Hyperaldosteronism - surgery
Kidney - physiology
Kinetics
Male
Mice
Rats
Rats, Sprague-Dawley
RNA, Messenger - genetics
RNA, Messenger - metabolism
Serine Endopeptidases - genetics
Serine Endopeptidases - physiology
Serine Endopeptidases - urine
Sodium Channels - metabolism
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Summary: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.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci0213229