title: Actions of cAMP on calcium sensitization in human detrusor smooth muscle contraction.
abstract: OBJECTIVE
  To clarify the effect of cAMP on the Ca(2+) -sensitized smooth muscle contraction in human detrusor, as well as the role of novel exchange protein directly activated by cAMP (Epac) in cAMP-mediated relaxation.
  
  
  METHODS
  All experimental protocols to record isometric tension force were performed using α-toxin-permeabilized human detrusor smooth muscle strips. The mechanisms of cAMP-mediated suppression of Ca(2+) sensitization activated by 10 μm carbachol (CCh) and 100 μm GTP were studied using a selective rho kinase (ROK) inhibitor, Y-27632, and a selective protein kinase C (PKC) inhibitor, GF-109203X. The relaxation mechanisms were further probed using a selective protein kinase A (PKA) activator, 6-Bnz-cAMP and a selective Epac activator, 8-pCPT-2'-O-Me-cAMP.
  
  
  RESULTS
  We observed that CCh-induced Ca(2+) sensitization was inhibited by cAMP in a concentration-dependent manner. GF-109203X (10 μm) but not Y-27632 (10 μm) significantly enhanced the relaxation effect induced by cAMP (100 μm). 6-Bnz-cAMP (100 μm) predominantly decreased the tension force in comparison with 8-pCPT-2'-O-Me-cAMP (100 μm).
  
  
  CONCLUSIONS
  We showed that cAMP predominantly inhibited the ROK pathway but not the PKC pathway. The PKA-dependent pathway is dominant, while Epac plays a minor role in human detrusor smooth muscle Ca(2+) sensitization.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kajioka
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.
authors.forename: Momoe
authors.initials: M
authors.lastname: Itsumi
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Urology, Faculty of Medicine and Health Sciences, Syarif Hidayaullah Jakarta State Islamic University, Jakarta, Indonesia.
authors.forename: Nouval
authors.initials: N
authors.lastname: Shahab
authors.affiliation: Urology Research Unit, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Ishigami
authors.affiliation: Urology Research Unit, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Innovation and Research Portfolio Planning, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
authors.affiliation: Division of Urology, Harasanshin Hospital, Fukuoka, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Yamaguchi
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D000368:Aged; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D000242:Cyclic AMP; D002118:Calcium
keywords: cAMP; calcium sensitization; human detrusor smooth muscle; permeabilization; rho kinase; α-toxin