title: Physiological Roles of Bradykinin and Involvement of Bradykinin B2 Receptor in Urethral Function in Humans and Animals.
abstract: OBJECTIVE
  We investigated the role of bradykinin in urethral function by examining contractile responses in urethral smooth muscle strips isolated from humans and the intraurethral pressure in rats and dogs.
  
  
  METHODS
  The contractile responses of human urethral tissue for bradykinin (0.01-10 µmol/L) were examined, and changes in intraurethral pressure induced by bradykinin (0.003-10 µg/kg) in anesthetized rats or dogs were measured. In addition, the effects of pretreatment with the bradykinin B2 receptor antagonist FK3657 were also examined.
  
  
  RESULTS
  In smooth muscle strips obtained from human urethra, bradykinin induced contraction, which was inhibited by FK3657 in a concentration-dependent manner. In anesthetized rats and dogs, intravenously administered bradykinin dose-dependently increased intraurethral pressure. FK3657 shifted the intraurethral pressure dose-response curve for bradykinin to the right in rats. The bradykinin-induced elevation of intraurethral pressure was also dose-dependently inhibited by FK3657 in dogs.
  
  
  CONCLUSIONS
  The present study provides evidence that bradykinin elicits urethral smooth muscle contraction via the bradykinin B2 receptor, suggesting the potential utility of this receptor as a novel target for the treatment of voiding dysfunction.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Yuyama
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeda
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000502:physiology*; D065094:Bradykinin B2 Receptor Antagonists / Q000494:pharmacology; D004285:Dogs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D011804:Quinolines / Q000494:pharmacology; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000502:physiology*; D014521:Urethra / Q000502:physiology*
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; C105311:FR 173657; D011804:Quinolines; D043782:Receptor, Bradykinin B2; D001920:Bradykinin
keywords: benign prostatic hyperplasia; bradykinin; urethral contraction