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10.1073/pnas.0702810104

http://scihub22266oqcxt.onion/10.1073/pnas.0702810104
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17804801!1976223!17804801
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suck abstract from ncbi


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pmid17804801      Proc+Natl+Acad+Sci+U+S+A 2007 ; 104 (37): 14849-54
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  • Renal expression of parvalbumin is critical for NaCl handling and response to diuretics #MMPMID17804801
  • Belge H; Gailly P; Schwaller B; Loffing J; Debaix H; Riveira-Munoz E; Beauwens R; Devogelaer JP; Hoenderop JG; Bindels RJ; Devuyst O
  • Proc Natl Acad Sci U S A 2007[Sep]; 104 (37): 14849-54 PMID17804801show ga
  • The distal convoluted tubule (DCT) plays an essential role in the reabsorption of NaCl by the kidney, a process that can be inhibited by thiazide diuretics. Parvalbumin (PV), a Ca(2+)-binding protein that plays a role in muscle fibers and neurons, is selectively expressed in the DCT, where its role remains unknown. We therefore investigated the renal phenotype of PV knockout mice (Pvalb(-/-)) vs. wild-type (Pvalb(+/+)) littermates. PV colocalized with the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) in the early DCT. The Pvalb(-/-) mice showed increased diuresis and kaliuresis at baseline with higher aldosterone levels and lower lithium clearance. Acute furosemide administration increased diuresis and natriuresis/kaliuresis, but, surprisingly, did not increase calciuria in Pvalb(-/-) mice. NaCl supplementation of Pvalb(-/-) mice increased calciuria at baseline and after furosemide. The Pvalb(-/-) mice showed no significant diuretic response to hydrochlorothiazide, but an accentuated hypocalciuria. A decreased expression of NCC was detected in the early DCT of Pvalb(-/-) kidneys in the absence of ultrastructural and apoptotic changes. The PV-deficient mice had a positive Ca(2+) balance and increased bone mineral density. Studies in mouse DCT cells showed that endogenous NCC expression is Ca(2+)-dependent and can be modulated by the levels of PV expression. These results suggest that PV regulates the expression of NCC by modulating intracellular Ca(2+) signaling in response to ATP in DCT cells. They also provide insights into the Ca(2+)-sparing action of thiazides and the pathophysiology of distal tubulopathies.
  • |Aldosterone/pharmacology[MESH]
  • |Animals[MESH]
  • |Bone Density[MESH]
  • |Calcium/analysis/urine[MESH]
  • |Cell Line, Transformed[MESH]
  • |Cells, Cultured[MESH]
  • |Diuresis[MESH]
  • |Diuretics/*pharmacology[MESH]
  • |Furosemide/pharmacology[MESH]
  • |Immunohistochemistry[MESH]
  • |Kidney Tubules, Distal/metabolism[MESH]
  • |Kidney/drug effects/*metabolism[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]
  • |Mice, Knockout[MESH]
  • |Parvalbumins/blood/*metabolism/urine[MESH]
  • |Potassium/urine[MESH]
  • |Sodium Chloride Symporter Inhibitors/adverse effects/*pharmacology[MESH]
  • |Sodium Chloride Symporters/physiology[MESH]
  • |Sodium/*metabolism/urine[MESH]


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