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Role of PKC α in Hypertonicity‐stimulated Urea Permeability
Author(s) -
Wang Yanhua,
Klein Janet D.,
Froehlich Otto,
Sands Jeff M.
Publication year - 2012
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.26.1_supplement.885.12
Subject(s) - protein kinase c , urea , endocrinology , medicine , chemistry , knockout mouse , stimulation , vasopressin , chelerythrine , biology , biochemistry , signal transduction , receptor
The ability of the kidney to concentrate urine is vitally important to our quality of life. In the hypertonic environment of the kidney, water and urea transporters must be regulated in a coordinated fashion to optimize function. We previously showed that hypertonicity increases urea permeability and the PKC blockers, chelerythrine and rottlerin, decreased hypertonicity‐stimulated urea permeability in rat inner medullary collecting ducts (IMCDs). Because PKCα knockout mice have a urine concentrating defect, we tested the effect of hypertonicity on urea permeability in mouse isolated perfused IMCDs. Increasing the osmolality of perfusate and bath from 290 to 690 mOsM did not change urea permeability (39±8 vs 42±8 ×10 −5 cm/s) in PKCα knockout mice, but significantly increased urea permeability (from 25±6 to 53±3 ×10 −5 cm/s) in wild‐type mice. To determine if the response to PKA was similarly missing in IMCDs of PKCα knockout mice, tubules were treated with 200 pm vasopressin (AVP) and subsequently with 200nM PKC stimulator PDBu. AVP stimulated urea permeability from 24±4 to 31±5 ×10 −5 cm/s in PKCα knockout mice. Unlike in rats, subsequent treatment of PDBu did not further increase urea permeability (from 31±5 to 32±5 ×10 −5 cm/s) in the PKCα knockout mice. Western blot analysis showed that expression of urea transporter, UT‐A1 in IMCDs was reduced in PKCα knockout mice compared to wild‐type mice. We conclude that PKCα regulates the hypertonicity‐related stimulation of urea transport but is not necessary for vasopressin stimulation of urea permeability in IMCDs.