title: Vacuolar H+-ATPase expression is increased in acid-secreting intercalated cells in kidneys of rats with hypercalcaemia-induced alkalosis.
abstract: OBJECTIVE
  Hypercalcaemia is known to be associated with systemic metabolic alkalosis, although the underlying mechanism is uncertain. Therefore, we aimed to examine whether hypercalcaemia was associated with changes in the expression of acid-base transporters in the kidney.
  
  
  METHODS
  Rats were infused with human parathyroid hormone (PTH, 15 microg kg(-1) day(-1)), or vehicle for 48 h using osmotic minipumps.
  
  
  RESULTS
  The rats treated with PTH developed hypercalcaemia and exhibited metabolic alkalosis (arterial HCO: 31.1 +/- 0.8 vs. 28.1 +/- 0.8 mmol L(-1) in controls, P < 0.05, n = 6), whereas the urine pH of 6.85 +/- 0.1 was significantly decreased compared with the pH of 7.38 +/- 0.1 in controls (P < 0.05, n = 12). The observed alkalosis was associated with a significantly increased expression of the B1-subunit of the H(+)-ATPase in kidney inner medulla (IM, 233 +/- 45% of the control level). In contrast, electroneutral Na(+)-HCO cotransporter NBCn1 and Cl(-)/HCO anion exchanger AE2 expression was markedly reduced in the inner stripe of the outer medulla (to 26 +/- 9% and 65 +/- 6%, respectively). These findings were verified by immunohistochemistry.
  
  
  CONCLUSIONS
  (1) hypercalcaemia-induced metabolic alkalosis was associated with increased urinary excretion of H(+); (2) the increased H(+)-ATPase expression in IM may partly explain the enhanced urinary acidification, which is speculated to prevent stone formation because of hypercalciuria and (3) the decreased expression of outer medullary AE2 suggests a compensatory reduction of the transepithelial bicarbonate transport.
authors: The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark.
authors: W
authors: W
authors: Wang
authors: J
authors: J
authors: Praetorius
authors: C
authors: C
authors: Li
authors: H A
authors: HA
authors: Praetorius
authors: T-H
authors: TH
authors: Kwon
authors: J
authors: J
authors: Frøkiaer
authors: S
authors: S
authors: Nielsen
mesh_terms: D000471:Alkalosis / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000032:analysis; D027321:Anion Transport Proteins / Q000032:analysis; D017920:Antiporters / Q000032:analysis; D027963:Chloride-Bicarbonate Antiporters / Q000032:analysis; D006934:Hypercalcemia / Q000097:blood / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D007263:Infusions, Parenteral; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D007672:Kidney Cortex / Q000201:enzymology / Q000378:metabolism; D007679:Kidney Medulla / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000008:administration & dosage; D006180:Proton-Translocating ATPases / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D064606:SLC4A Proteins; D027982:Sodium-Bicarbonate Symporters / Q000032:analysis; D000076988:Sulfate Transporters; D014617:Vacuoles / Q000201:enzymology
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D027321:Anion Transport Proteins; D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D010281:Parathyroid Hormone; D064606:SLC4A Proteins; C494615:Slc26A4 protein, rat; C422004:Slc4a4 protein, rat; C498902:Slc4a7 protein, rat; D027982:Sodium-Bicarbonate Symporters; D000076988:Sulfate Transporters; D006180:Proton-Translocating ATPases