Urinary prostasin in humans: relationships among prostasin, aldosterone and epithelial sodium channel activity.
Prostasin, a membrane-bound serine protease, is known to increase the activity of the epithelial sodium channel (ENaC). Gene expression of prostasin was shown to be regulated by aldosterone, which increases the rate of sodium reabsorption through ENaC. To clarify the physiological relationships among prostasin, aldosterone and ENaC, we developed a specific radioimmunoassay (RIA) for human prostasin. Prostasin levels in urine were determined in 26 normotensive and 121 hypertensive subjects. Aldosterone content in urine and plasma, urinary Na/K ratio and other clinical parameters were also measured. We observed a highly significant correlation between prostasin and aldosterone concentration in urine (correlation coefficient: 0.673, P<0.0001). A significant correlation was also found between urinary prostasin and plasma aldosterone concentration (correlation coefficient: 0.229, P<0.05). In addition, urinary prostasin excretion was inversely correlated with urinary Na/K ratio (correlation coefficient: -0.425, P<0.0001). In conclusion, we developed a prostasin-specific RIA and applied it to the clinical study. Our findings suggest that urinary prostasin level is strongly correlated with urinary or plasma aldosterone level and may serve as a surrogate marker for ENaC activation in hypertensive patients. However, it is not clear, at the present time, whether endogenous aldosterone regulates prostasin expression or vice versa.
Koda
Aya
A
Novartis Institute for BioMedical Research, Tsukuba, Ibaraki, Japan.
Wakida
Naoki
N
Toriyama
Kazuhiro
K
Yamamoto
Kazutoshi
K
Iijima
Hiromi
H
Tomita
Kimio
K
Kitamura
Kenichiro
K
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000378:metabolism*; D015153:Blotting, Western; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D011994:Recombinant Proteins; D012697:Serine Endopeptidases / Q000737:chemistry / Q000652:urine*; D055815:Young Adult; D000099271:Prostasin
D000450:Aldosterone; D053503:Epithelial Sodium Channels; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D000099271:Prostasin