| First Author | Wang Y | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 304 |
| Issue | 2 | Pages | F233-8 |
| PubMed ID | 23097465 | Mgi Jnum | J:192175 |
| Mgi Id | MGI:5464139 | Doi | 10.1152/ajprenal.00484.2012 |
| Citation | Wang Y, et al. (2013) Role of protein kinase C-alpha in hypertonicity-stimulated urea permeability in mouse inner medullary collecting ducts. Am J Physiol Renal Physiol 304(2):F233-8 |
| abstractText | The kidney's ability to concentrate urine is vitally important to our quality of life. In the hypertonic environment of the kidney, urea transporters must be regulated to optimize function. We previously showed that hypertonicity increases urea permeability and that the protein kinase C (PKC) blockers chelerythrine and rottlerin decreased hypertonicity-stimulated urea permeability in rat inner medullary collecting ducts (IMCDs). Because PKCalpha knockout (PKCalpha(-/-)) mice have a urine-concentrating defect, we tested the effect of hypertonicity on urea permeability in isolated perfused mouse IMCDs. Increasing the osmolality of perfusate and bath from 290 to 690 mosmol/kgH(2)O did not change urea permeability in PKCalpha(-/-) mice but significantly increased urea permeability in wild-type mice. To determine whether the response to protein kinase A was also missing in IMCDs of PKCalpha(-/-) mice, tubules were treated with vasopressin and subsequently with the PKC stimulator phorbol dibutyrate (PDBu). Vasopressin stimulated urea permeability in PKCalpha(-/-) mice. Like vasopressin, forskolin stimulated urea permeability in PKCalpha(-/-) mice. We previously showed that, in rats, vasopressin and PDBu have additive stimulatory effects on urea permeability. In contrast, in PKCalpha(-/-) mice, PDBu did not further increase vasopressin-stimulated urea permeability. Western blot analysis showed that expression of the UT-A1 urea transporter in IMCDs was increased in response to vasopressin in wild-type mice as well as PKCalpha(-/-) mice. Hypertonicity increased UT-A1 phosphorylation in wild-type mice but not in PKCalpha(-/-) mice. We conclude that PKCalpha mediates hypertonicity-stimulated urea transport but is not necessary for vasopressin stimulation of urea permeability in mouse IMCDs. |
