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Downregulation of key renal acid base transport proteins are associated with urinary acidification defect in response to urinary tract obstruction.
Author(s) -
Wang Guixian,
Li Chunling,
Kim SooWan,
Djurhuus Jens Christian,
Nielsen Soren,
Frokiaer Jorgen
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1414-a
Subject(s) - cotransporter , downregulation and upregulation , urinary system , acidosis , endocrinology , nephron , medicine , sodium–hydrogen antiporter , metabolic acidosis , symporter , acid–base homeostasis , chemistry , pendrin , kidney , bumetanide , intercalated cell , transporter , biology , biochemistry , sodium , organic chemistry , gene
Urinary tract obstruction impairs renal function and is often associated with a urinary acidification defect. This is caused by diminished net H + secretion and/or HCO 3 − reabsorbtion. To identify the molecular mechanismsof these defects, expression levels of key acid‐base transporters along the renal nephron and collecting duct of rat kidneys were examined in response to 24‐h bilateral ureteral obstruction (BUO), 4 days after release of BUO (BUO‐R), and BUO‐R rats subjected to experimental metabolic acidosis obtained by oral NH 4 Cl loading (BUO‐A). Immunoblot analysis revealed that BUO induced significant downregulation of the type 3 Na + /H + exchanger (NHE3) to 21 ±4%, the electrogenic Na + /HCO 3 − cotransporter (NBC1) to 71 ± 5%, the type 1 bumetanide‐sensitive Na + ‐K + ‐2Cl − cotransporter (NKCC2) to 3 ± 1%, the electroneutral Na + /HCO 3 − cotransporter (NBCn1) to 46±7%, and the anion exchanger (pendrin) to 87 ± 2%. These changes were confirmed by immunocytochemistry. BUO‐R was associated with persistant downregulation of these transporters. In addition, the H + ATPase (B1‐subunit) was markedly downregulated in the renal medulla. In BUO‐A rats, plasma pH and HCO 3 − levels were dramatically reduced after 2 days of NH 4 Cl loading demonstrating a urinary acidification defect. In conclusion, downregulation of key renal acid‐base transporters in response to BUO and release of BUO are likely to contribute to the apparent urinary acidification defect in response to urinary tract obstruction.