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Hypertonicity Increases Urea Permeability through PKC in Inner Medullary Collecting Ducts
Author(s) -
Wang Yanhua,
Klein Janet D.,
Sands Jeff M.
Publication year - 2010
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.24.1_supplement.1024.20
Subject(s) - protein kinase c , urea , chelerythrine , medicine , endocrinology , chemistry , phorbol , permeability (electromagnetism) , rottlerin , phosphorylation , biology , biochemistry , membrane
We showed that hypertonicity increases urea permeability as well as UT‐A1 phosphorylation and biotinylation in the inner medullary collect duct (IMCD). We also showed that increases in hypertonicity do not increase cAMP in IMCD, but do increase Ca2+ suggesting involvement of a Ca‐dependent protein kinase in the urea transport response. To further investigate the signaling pathways that might be involved in the response to hypertonicity, we tested the effect of PKC inhibitors on urea permeability in isolated perfused IMCDs. Increasing the osmolality of perfusate and bath from 290 to 690mOsM significantly stimulated urea permeability from 24±2 to 49±4 ×10 −5 cm/s and was returned to control levels by inhibition of PKC with 10μM chelerythrine or 50μM rottlerin. To determine the potential synergy between AVP and PKC, phorbol dibutyrate (PDBu), was used to stimulate PKC. AVP stimulated urea permeability from 21±2 to 74±16 ×10 −5 cm/s. PDBu alone did not change the basal urea permeability. In the presence of AVP, however, PDBu significantly increased urea permeability from 74±16 to 94±18 ×10 −5 cm/s. The AVP and PDBu‐stimulated urea permeability was reduced by 10μM chelerythrine to AVP alone levels. We conclude that hypertonicity stimulates UT‐A1 through a PKC‐mediated phosphorylation. Whether PKC directly phosphorylates UT‐A1 or acts through a cascade remains to be determined. Supported by NIH RO1‐DK41707.