title: Modulation of 11β-hydroxysteroid dehydrogenase 1 by β2-adrenoceptor in the ischaemia-reperfused rat kidney.
abstract: BACKGROUND
  11β-Hydroxysteroid dehydrogenase Type 1 (11βHSD-1) amplifies intracellular levels of active glucocorticoids which possess protective effects against organ ischaemia and reperfusion (I/R). However, the mechanisms by which 11βHSD-1 is modified after a renal I/R challenge remain unclear. This study investigated the effect of β(2)-adrenoceptor (β(2)-AR) activation and the subsequent signalling pathways on renal 11βHSD-1 gene expression following renal I/R.
  
  
  METHODS
  Renal I/R was induced using 25 min of bilateral renal artery occlusion in 4-week-old Wistar rats followed by an intraperitoneal injection of various doses of adeno-β(2)-AR gene. Following renal I/R, kidneys, plasma and urine were collected to assay 11βHSD messenger RNA (mRNA) levels, β(2)-AR signalling cascades and renal function.
  
  
  RESULTS
  On the second day after the renal I/R challenge, there was a reduction in renal 11βHSD-1 mRNA levels associated with a decrease in stimulatory G protein α (Gsα) and adenylate cyclase-1 (ACY-1) in the kidney. The addition of the adeno-β(2)-AR gene resulted in greater increases in 11βHSD-1 mRNA and β(2)-AR-Gsα-ACY-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) activity in the kidney but had no effect on 11βHSD-2 mRNA or protein kinase C levels in the kidney.
  
  
  CONCLUSIONS
  Over-expression of β(2)-AR resulting from the gene delivery improved renal function and 11βHSD-1 production following renal I/R, which were actions exerted through the cAMP-PKA pathway. The stimulatory effect of functional β(2)-AR activation on renal 11βHSD-1 expression may offer a means of protection from renal I/R injury.
authors.affiliation: Department of Pediatrics, Central Experimental Animal Center, Teikyo University School of Medicine, Tokyo, Japan. akio@med.teikyo-u.ac.jp
authors.forename: Akio
authors.initials: A
authors.lastname: Nakamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyagawa
authors.forename: Yukishige
authors.initials: Y
authors.lastname: Yanagawa
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C