Urinary prostasin in humans: relationships among prostasin, aldosterone and epithelial sodium channel activity
Urinary prostasin in humans: relationships among prostasin, aldosterone and epithelial sodium channel activity
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DOI：
10.1038/hr.2009.6
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发表时间：
2009-04-01
影响因子：
5.4
通讯作者：
Kitamura, Kenichiro
中科院分区：
文献类型：
--
作者：
Koda, Aya;Wakida, Naoki;Kitamura, Kenichiro
前列腺素是一种膜结合丝氨酸蛋白酶，已知其可增加上皮钠通道（ENaC）的活性。前列腺素的基因表达被证明是由醛固酮调节的，醛固酮通过ENaC增加钠重吸收的速率。为了阐明前列腺素、醛固酮和ENaC之间的生理关系，我们建立了人前列腺素的特异性放射免疫分析法（RIA）。测定了26例正常血压者和121例高血压者的尿前列腺素水平。同时测定尿、血浆醛固酮含量、尿Na/K比值等临床指标。尿前列腺素与尿醛固酮浓度呈高度显著相关（r = 0.673，P < 0.0001）。尿前列腺素与血浆醛固酮浓度呈显著相关（r = 0.229，P < 0.05）。尿前列腺素排泄量与尿钠钾比值呈负相关（r =-0.425，P < 0.0001）。总之，我们建立了前列腺素特异性放射免疫分析法，并将其应用于临床研究。我们的研究结果表明，尿前列腺素水平与尿或血浆醛固酮水平密切相关，可作为高血压患者ENaC激活的替代指标。然而，目前尚不清楚内源性醛固酮是否调节前列腺素的表达，反之亦然。
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.