title: Glucocorticoids enhance the expression of the basolateral Na+:HCO3- cotransporter in renal proximal tubules.
abstract: BACKGROUND
  Studies have shown that glucocorticoids enhance HCO3- reabsorption in proximal tubules. Functional and molecular studies indicate that HCO3- reabsorption in proximal tubules is mediated via luminal H(+)-ATPase and Na+/H+ exchanger (NHE-3), and basolateral Na+:HCO3- cotransporter (NBC) acting in series. The purpose of these experiments was to examine the effect of adrenal steroids on NBC-1 and NHE-3 expression and activity in rat renal proximal tubules.
  
  
  METHODS
  Rats were injected subcutaneously with dexamethasone (100 mu/day) or deoxycorticosterone acetate (30 mg/kg), potent glucocorticoid, or mineralocorticoid analogues, respectively. Animals were sacrificed after two or four days, and NBC-1 and NHE-3 mRNA expression and activities were measured in cortex and proximal tubules.
  
  
  RESULTS
  Northern hybridizations indicated that cortical NBC-1 mRNA expression increased by approximately 92% in rats treated with dexamethasone for four days (N = 6, P < 0.03) but not two days. NHE-3 mRNA expression remained unchanged. NBC and NHE-3 activities were measured as the Na-dependent pHi recovery from an acid load in the presence or absence of HCO3-, respectively, and appropriate inhibitors in proximal tubule suspensions loaded with BCECF. NBC activity increased by approximately 80% in rats treated with dexamethasone for four days (P < 0.01, N = 5) but not two days. NHE-3 activity increased by 34 and 42% in rats treated with dexamethasone for two and four days, respectively (P < 0.05 and P < 0.02 for each group vs. control). Treatment with deoxycorticosterone acetate did not alter NBC-1 expression.
  
  
  CONCLUSIONS
  Glucocorticoids at pharmacologic concentrations enhance the mRNA expression and functional activity of renal proximal tubule NBC-1. Enhanced NBC and NHE-3 activities could result in increased HCO3- reabsorption in proximal tubule and could contribute to the maintenance of metabolic alkalosis in pathophysiologic states associated with increased glucocorticoid production.
authors.affiliation: Department of Internal Medicine, University of Cincinnati, Ohio, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ali
authors.forename: H
authors.initials: H
authors.lastname: Amlal
authors.forename: C E
authors.initials: CE
authors.lastname: Burnham
authors.forename: M
authors.initials: M
authors.lastname: Soleimani
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D007672:Kidney Cortex / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027982:Sodium-Bicarbonate Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D005938:Glucocorticoids; D012333:RNA, Messenger; C000613387:Slc9a3 protein, rat; D027982:Sodium-Bicarbonate Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D003900:Desoxycorticosterone; D003907:Dexamethasone