title: Responses to diuretic treatment in gene-targeted mice lacking serum- and glucocorticoid-inducible kinase 1.
abstract: OBJECTIVE
  Serum- and glucocorticoid-inducible kinase 1 (SGK1) stimulates the epithelial sodium channel (ENaC), renal outer medullary K(+) channel 1, Na(+)/K(+)-ATPase and presumably the Na(+)-Cl(-) cotransporter (NCC). SGK1-deficient mice (sgk(-/-)) show a compensated salt-losing phenotype with secondary hyperaldosteronism. The present experiments explored the role of SGK1 in the response to diuretics.
  
  
  METHODS
  sgk1(-/-) mice and their wild-type littermates (sgk1(+/+)) were treated with the ENaC blocker triamterene (200 mg/l), the Na(+)-K(+)-2Cl(-) cotransport inhibitor furosemide (125 mg/l), the NCC blocker hydrochlorothiazide (400 mg/l) and the mineralocorticoid receptor blocker canrenoate (800 mg/l) for 8 days. Renal SGK1 expression was studied using quantitative RT-PCR and immunofluorescence.
  
  
  RESULTS
  Diuretic treatment increased SGK1 mRNA and protein expression in the kidney of wild-type sgk1(+/+) mice. The responses to furosemide, hydrochlorothiazide or canrenoate were not different between sgk1(+/+) and sgk1(-/-) mice, and were accompanied by moderate increases in plasma aldosterone and urea concentrations. However, treatment with triamterene in sgk1(-/-) mice (but not in sgk1(+/+) mice) led to severe, eventually lethal, body weight loss as well as increases in plasma aldosterone, urea and K(+) concentrations.
  
  
  CONCLUSIONS
  SGK1 is required for diuretic tolerance to triamterene. The observations confirm the impaired kaliuretic potency of sgk1(-/-) mice and point to a role of SGK1 in renal Na(+) reabsorption by mechanisms other than ENaC.
authors.affiliation: Department of Physiology, University of Tubingen, Tubingen, Germany.
authors.forename: Ferruh
authors.initials: F
authors.lastname: Artunc
authors.forename: Ammar
authors.initials: A
authors.lastname: Ebrahim
authors.forename: Balasaheb
authors.initials: B
authors.lastname: Siraskar
authors.forename: Omaima
authors.initials: O
authors.lastname: Nasir
authors.forename: Rexhep
authors.initials: R
authors.lastname: Rexhepaj
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Bjoern
authors.initials: B
authors.lastname: Friedrich
authors.forename: Teut
authors.initials: T
authors.lastname: Risler
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D004361:Drug Tolerance; D004435:Eating / Q000187:drug effects / Q000502:physiology; D053503:Epithelial Sodium Channels / Q000502:physiology; D018390:Gene Targeting / Q000379:methods*; D017874:Immediate-Early Proteins / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D014223:Triamterene / Q000494:pharmacology; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D004232:Diuretics; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D014223:Triamterene; D000099184:Serum-Glucocorticoid Regulated Kinases