Regulation by glucocorticoids of expression and activity of rBSC1, the Na+-K+(NH4+)-2Cl- cotransporter of medullary thick ascending limb

J Biol Chem. 2000 Oct 27;275(43):33548-53. doi: 10.1074/jbc.M006591200.


To assess whether glucocorticoids regulate rBSC1, the apical Na(+)-K(+)(NH(4)(+))-2Cl(-) cotransporter of kidney medullary thick ascending limb (MTAL), studies were performed in normal rats, adrenalectomized (ADX) rats, and ADX rats infused with dexamethasone for 6 days. The effects of dexamethasone on rBSC1 were also studied in vitro using isolated rat MTAL segments. Cotransport activity was estimated by intracellular pH measurements; rBSC1 protein was quantified in MTAL crude membranes by immunoblotting analysis, and mRNA was quantified by quantitative reverse transcription-polymerase chain reaction. The abundance of rBSC1 protein and mRNA increased in ADX rats infused with dexamethasone compared with ADX rats (p < 0. 04). In addition, application of dexamethasone for 1-3 h to MTALs caused rBSC1 protein and mRNA abundance and cotransport activity to significantly increase in a hyperosmotic medium (450 mosmol/kg of H(2)O) containing 0.7 nm arginine vasopressin, which is an in vitro experimental condition that resembles the in vivo MTAL environment. Results obtained in various media and with 8-bromo-cAMP indicated that stimulation of rBSC1 expression by glucocorticoids required interactions between glucocorticoid receptor- and cAMP-dependent factors. Up to 100 nm d-aldosterone had no effect on cotransport activity in vitro. Thus glucocorticoids directly stimulate MTAL rBSC1 expression and activity, which contributes to glucocorticoid-dependent effects on the renal regulation of acid-base balance and urinary concentrating ability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenalectomy
  • Animals
  • Arginine Vasopressin / pharmacology
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Dexamethasone / pharmacology*
  • Kidney Medulla / metabolism*
  • Kidney Tubules / metabolism*
  • Male
  • Quaternary Ammonium Compounds / metabolism
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Potassium-Chloride Symporters


  • Carrier Proteins
  • Quaternary Ammonium Compounds
  • RNA, Messenger
  • Sodium-Potassium-Chloride Symporters
  • Arginine Vasopressin
  • Dexamethasone