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10.1074/jbc.M111.222968

http://scihub22266oqcxt.onion/10.1074/jbc.M111.222968
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suck abstract from ncbi


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pmid21737451      J+Biol+Chem 2011 ; 286 (34): 30200-10
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  • Activation of the bumetanide-sensitive Na+,K+,2Cl- cotransporter (NKCC2) is facilitated by Tamm-Horsfall protein in a chloride-sensitive manner #MMPMID21737451
  • Mutig K; Kahl T; Saritas T; Godes M; Persson P; Bates J; Raffi H; Rampoldi L; Uchida S; Hille C; Dosche C; Kumar S; Castaneda-Bueno M; Gamba G; Bachmann S
  • J Biol Chem 2011[Aug]; 286 (34): 30200-10 PMID21737451show ga
  • 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.
  • |Animals[MESH]
  • |Antidiuretic Agents/pharmacology[MESH]
  • |Cell Line, Transformed[MESH]
  • |Chlorides/*metabolism[MESH]
  • |Deamino Arginine Vasopressin/pharmacology[MESH]
  • |Kidney Tubules, Distal/*metabolism[MESH]
  • |Mice[MESH]
  • |Mice, Knockout[MESH]
  • |Osmotic Pressure[MESH]
  • |Phosphorylation/drug effects/physiology[MESH]
  • |Rabbits[MESH]
  • |Receptors, Vasopressin/genetics/metabolism[MESH]
  • |Sodium-Potassium-Chloride Symporters/genetics/*metabolism[MESH]
  • |Solute Carrier Family 12, Member 1[MESH]
  • |Uromodulin/genetics/*metabolism[MESH]


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