@article{MutigKahlSaritasetal.2011,
  author    = {Mutig, Kerim and Kahl, Thomas and Saritas, Turgay and Godes, Michael and Persson, Pontus and Bates, James and Raffi, Hajamohideen and Rampoldi, Luca and Uchida, Shinichi and Hille, Carsten and Dosche, Carsten and Kumar, Satish and Castaneda-Bueno, Maria and Gamba, Gerardo and Bachmann, Sebastian},
  title     = {Activation of the Bumetanide-sensitive Na+, K+,2Cl(-) Cotransporter (NKCC2) Is Facilitated by Tamm-Horsfall Protein in a Chloride-sensitive Manner},
  series = {The journal of biological chemistry},
  volume    = {286},
  journal   = {The journal of biological chemistry},
  number    = {34},
  publisher = {American Society for Biochemistry and Molecular Biology},
  address   = {Bethesda},
  issn      = {0021-9258},
  doi       = {10.1074/jbc.M111.222968},
  pages     = {30200 -- 30210},
  year      = {2011},
  abstract  = {Active transport of NaCl across thick ascending limb (TAL) epithelium is accomplished by Na+, K+,2Cl(-) cotransporter (NKCC2). The activity of NKCC2 is determined by vasopressin (AVP) or intracellular chloride concentration and includes its amino-terminal phosphorylation. Co-expressed Tamm-Horsfall protein (THP) has been proposed to interact with NKCC2. We hypothesized that THP modulates NKCC2 activity in TAL. THP-deficient mice (THP-/-) showed an increased abundance of intracellular NKCC2 located in subapical vesicles (+47\% compared with wild type (WT) mice), whereas base-line phosphorylation of NKCC2 was significantly decreased (-49\% compared with WT mice), suggesting reduced activity of the transporter in the absence of THP. Cultured TAL cells with low endogenous THP levels and low base-line phosphorylation of NKCC2 displayed sharp increases in NKCC2 phosphorylation (+38\%) along with a significant change of intracellular chloride concentration upon transfection with THP. In NKCC2-expressing frog oocytes, co-injection with THP cRNA significantly enhanced the activation of NKCC2 under low chloride hypotonic stress (+112\% versus +235\%). Short term (30 min) stimulation of the vasopressin V2 receptor pathway by V2 receptor agonist (deamino-cis-D-Arg vasopressin) resulted in enhanced NKCC2 phosphorylation in WT mice and cultured TAL cells transfected with THP, whereas in the absence of THP, NKCC2 phosphorylation upon deamino-cis-D-Arg vasopressin was blunted in both systems. Attenuated effects of furosemide along with functional and structural adaptation of the distal convoluted tubule in THP-/- mice supported the notion that NaCl reabsorption was impaired in TAL lacking THP. In summary, these results are compatible with a permissive role for THP in the modulation of NKCC2-dependent TAL salt reabsorptive function.},
  language  = {en}
}
@article{SchildrothRettigZimmermannKalketal.2011,
  author    = {Schildroth, Janice and Rettig-Zimmermann, Juliane and Kalk, Philipp and Steege, Andreas and Faehling, Michael and Sendeski, Mauricio and Paliege, Alexander and Lai, En Yin and Bachmann, Sebastian and Persson, Pontus B. and Hocher, Berthold and Patzak, Andreas},
  title     = {Endothelin type A and B receptors in the control of afferent and efferent arterioles in mice},
  series = {Nephrology, dialysis, transplantation},
  volume    = {26},
  journal   = {Nephrology, dialysis, transplantation},
  number    = {3},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0931-0509},
  doi       = {10.1093/ndt/gfq534},
  pages     = {779 -- 789},
  year      = {2011},
  abstract  = {Background. Endothelin 1 contributes to renal blood flow control and pathogenesis of kidney diseases. The differential effects, however, of endothelin 1 (ET-1) on afferent (AA) and efferent arterioles (EA) remain to be established. Methods. We investigated endothelin type A and B receptor (ETA-R, ETB-R) functions in the control of AA and EA. Arterioles of ETB-R deficient, rescued mice [ETB (-/-)] and wild types [ETB(+/+)] were microperfused. Results. ET-1 constricted AA stronger than EA in ETB (-/-) and ETB(+/+) mice. Results in AA: ET-1 induced similar constrictions in ETB(-/-) and ETB(+/+) mice. BQ-123 (ETA-R antagonist) inhibited this response in both groups. ALA-ET-1 and IRL1620 (ETB-R agonists) had no effect on arteriolar diameter. L-NAME did neither affect basal diameters nor ET-1 responses. Results in EA: ET-1 constricted EA stronger in ETB(+/+) compared to ETB(-/-). BQ-123 inhibited the constriction completely only in ETB(-/-). ALA-ET-1 and IRL1620 constricted only arterioles of ETB(+/+) mice. L-NAME decreased basal diameter in ETB(+/+), but not in ETB(-/-) mice and increased the ET-1 response similarly in both groups. The L-NAME actions indicate a contribution of ETB-R in basal nitric oxide (NO) release in EA and suggest dilatory action of ETA-R in EA. Conclusions. ETA-R mediates vasoconstriction in AA and contributes to vasoconstriction in EA in this mouse model. ETB-R has no effect in AA but mediates basal NO release and constriction in EA. The stronger effect of ET-1 on AA supports observations of decreased glomerular filtration rate to ET-1 and indicates a potential contribution of ET-1 to the pathogenesis of kidney diseases.},
  language  = {en}
}