title: Involvement of stretch-induced Rho-kinase activation in the generation of bladder tone.
abstract: OBJECTIVE
  The present study investigated the role of the Rho-kinase (ROK) pathway in the maintenance of bladder tone during the storage phase, and its effects on bladder compliance.
  
  
  METHODS
  Muscle strips from isolated rat bladder (detrusor strips) were used to evaluate the effects of the ROK inhibitors Y-27632 and HA-1077 on resting tension, which is independent of G-protein coupled pathways. Stretch-induced ROK activation was assessed by measuring phosphorylation of MYPT1 (myosin phosphatase targeting subunit) using Western blotting. The effect of ROK inhibitors on bladder compliance during bladder filling was assessed in an in vitro whole bladder model.
  
  
  RESULTS
  Y-27632 and HA-1077 caused concentration-dependent relaxation of detrusor strips. Stretch increased MYPT1-p[Thr853] levels by approximately 1.5-fold in normal Krebs buffer. The ROK inhibitor Y-27632 abolished the stretch-induced increase and reduced the level of MYPT1-p[Thr853] to <50% of the basal values in normal Krebs buffer. Stretch-induced phosphorylation of MYPT1 was independent of Ca(2+) originating from either extracellular or intracellular stores. When tested in the isolated whole rat bladder model, HA-1077 significantly increased bladder compliance at both 3 and 10 µM.
  
  
  CONCLUSIONS
  This study demonstrates that the ROK pathway is constitutively active and stretch further activates the ROK pathway, which contributes to the generation of bladder tone, thereby affecting bladder compliance.
authors.affiliation: Department of Urology, Fukushima Medical University, Fukushima, Japan. shioaji999@gmail.com
authors.forename: Homare
authors.initials: H
authors.lastname: Shiomi
authors.forename: Norio
authors.initials: N
authors.lastname: Takahashi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ogawa
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Haga
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kushida
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomiya
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Yanagida
authors.forename: Kei
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Ken
authors.initials: K
authors.lastname: Aikawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003187:Compliance; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology* / Q000294:innervation*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054645:Protein Phosphatase 1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012026:Reflex, Stretch / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects / Q000201:enzymology* / Q000294:innervation*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D002118:Calcium
keywords: Rho-kinase; compliance; storage phase; stretch