Published Online
on September 19, 2005

A more recent version of this article appeared on October 1, 2005

This Article Full Text (PDF) All Versions of this Article: 46/4/683    most recent 01.HYP.0000184108.12155.6bv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Olivieri, O. Articles by Righetti, P. G. Search for Related Content PubMed PubMed Citation Articles by Olivieri, O. Articles by Righetti, P. G. Related Collections Hypertension - basic studies Ion channels/membrane transport

Submitted on July 18, 2005
Revised on August 7, 2005

Urinary Prostasin. A Candidate Marker of Epithelial Sodium Channel Activation in Humans

Oliviero Olivieri^*; Annalisa Castagna; Patrizia Guarini; Laura Chiecchi; Gherardo Sabaini; Francesca Pizzolo; Roberto Corrocher; and Pier Giorgio Righetti

From the Department of Clinical and Experimental Medicine, Unit of Internal Medicine (O.O., A.C., P.G., L.C., F.P., R.C.), and Department of Science and Technology (A.C., G.S., P.G.R.), University of Verona, Italy.

^* To whom correspondence should be addressed. E-mail: oliviero.olivieri{at}univr.it.

Abstract--Prostasin is a serine peptidase hypothesized to regulate epithelial sodium channel (ENaC) activity in animals or on in vitro cultured cells. We investigated whether urinary prostasin may be a candidate marker of ENaC activation in humans. We studied 10 healthy volunteers and 8 hypertensive patients with raised aldosterone-to-renin ratio before and after spironolactone or saline/Florinef suppression test, respectively. Four healthy subjects were also studied before and after saline. Urinary prostasin was evaluated by SDS-PAGE, 2D maps, and Western blotting. Every sample of normotensive individuals was compared with the corresponding sample of urine collected after spironolactone or saline; every sample of hypertensive patients was compared with the corresponding sample of urine collected after saline or Florinef. Prostasin was detectable in all subjects regardless of gender, dietary sodium intake, and spironolactone treatment. Spironolactone (100 mg) increased urinary Na⁺/K⁺ ratio and decreased urinary prostasin in normotensives in whom the renin/aldosterone axis was activated by a low Na⁺ intake, but it was ineffective in individuals with high Na⁺ intake. Saline infusion also reduced prostasin in normotensive subjects. In contrast, prostasin paradoxically increased in urine of patients affected by primary aldosteronism after volume expansion. By 2D immunoblotting, several protein isoforms were observed, some of them being overexpressed after inhibition tests in patients with primary aldosteronism. In addition to a "basal" aliquot of prostasin, constitutively released in human urine regardless of sodium balance and aldosterone activation, there exists a second "aldosterone-responsive" aliquot modulated by Na⁺ intake and potentially suitable as candidate marker of ENaC activation.

Key words: aldosterone • renin • sodium • ions • mineralocorticoids • hypertension • sodium channels

This article has been cited by other articles:

				P. Svenningsen, T. R. Uhrenholt, Y. Palarasah, K. Skjodt, B. L. Jensen, and O. Skott Prostasin-dependent activation of epithelial Na+ channels by low plasmin concentrations Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2009; 297(6): R1733 - R1741. [Abstract] [Full Text] [PDF]

				K. Bramham, H.D. Mistry, L. Poston, L.C. Chappell, and A.J. Thompson The non-invasive biopsy--will urinary proteomics make the renal tissue biopsy redundant? QJM, August 1, 2009; 102(8): 523 - 538. [Abstract] [Full Text] [PDF]

				E. J. Hoorn, N. van der Lubbe, and R. Zietse The renal WNK kinase pathway: a new link to hypertension Nephrol. Dial. Transplant., April 1, 2009; 24(4): 1074 - 1077. [Full Text] [PDF]

				P. Svenningsen, C. Bistrup, U. G. Friis, M. Bertog, S. Haerteis, B. Krueger, J. Stubbe, O. N. Jensen, H. C. Thiesson, T. R. Uhrenholt, et al. Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel J. Am. Soc. Nephrol., February 1, 2009; 20(2): 299 - 310. [Abstract] [Full Text] [PDF]

				V. Nesterov, A. Dahlmann, M. Bertog, and C. Korbmacher Trypsin can activate the epithelial sodium channel (ENaC) in microdissected mouse distal nephron Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1052 - F1062. [Abstract] [Full Text] [PDF]

				A. Diakov, K. Bera, M. Mokrushina, B. Krueger, and C. Korbmacher Cleavage in the {gamma}-subunit of the epithelial sodium channel (ENaC) plays an important role in the proteolytic activation of near-silent channels J. Physiol., October 1, 2008; 586(19): 4587 - 4608. [Abstract] [Full Text] [PDF]

				G. M. Verghese, M. F. Gutknecht, and G. H. Caughey Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchor Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1258 - C1270. [Abstract] [Full Text] [PDF]

				H.-Y. Lin, H. Zhang, Q. Yang, H.-X. Wang, H.-M. Wang, K. X. Chai, L.-M. Chen, and C. Zhu Expression of Prostasin and Protease Nexin-1 in Rhesus Monkey (Macaca mulatta) Endometrium and Placenta During Early Pregnancy J. Histochem. Cytochem., October 1, 2006; 54(10): 1139 - 1147. [Abstract] [Full Text] [PDF]