title: Pre- and post-junctional bradykinin B2 receptors regulate smooth muscle tension to the pig intravesical ureter.
abstract: OBJECTIVE
  Neuronal and non-neuronal bradykinin (BK) receptors regulate the contractility of the bladder urine outflow region. The current study investigates the role of BK receptors in the regulation of the smooth muscle contractility of the pig intravesical ureter.
  
  
  METHODS
  Western blot and immunohistochemistry were used to show the expression of BK B1 and B2 receptors and myographs for isometric force recordings.
  
  
  RESULTS
  B2 receptor expression was consistently detected in the intravesical ureter urothelium and smooth muscle layer, B1 expression was not detected where a strong B2 immunoreactivity was observed within nerve fibers among smooth muscle bundles. On ureteral strips basal tone, BK induced concentration-dependent contractions, were potently reduced by extracellular Ca(2+) removal and by B2 receptor and voltage-gated Ca(2+) (VOC) channel blockade. BK contraction did not change as a consequence of urothelium mechanical removal or cyclooxygenase and Rho-associated protein kinase inhibition. On 9,11-dideoxy-9a,11a-methanoepoxy prostaglandin F2α (U46619)-precontracted samples, under non-adrenergic non-cholinergic (NANC) and nitric oxide (NO)-independent NANC conditions, electrical field stimulation-elicited frequency-dependent relaxations which were reduced by B2 receptor blockade. Kallidin, a B1 receptor agonist, failed to increase preparation basal tension or to induce relaxation on U46619-induced tone.
  
  
  CONCLUSIONS
  The present results suggest that BK produces contraction of pig intravesical ureter via smooth muscle B2 receptors coupled to extracellular Ca(2+) entry mainly via VOC (L-type) channels. Facilitatory neuronal B2 receptors modulating NO-dependent or independent NANC inhibitory neurotransmission are also demonstrated.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Ana S F
authors.initials: AS
authors.lastname: Ribeiro
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Vítor S
authors.initials: VS
authors.lastname: Fernandes
authors.affiliation: Departamento de Anatomía y Anatomía Patológica Comparadas, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Martínez
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: María Elvira
authors.initials: ME
authors.lastname: López-Oliva
authors.affiliation: Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Barahona
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Paz
authors.initials: P
authors.lastname: Recio
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Martínez
authors.affiliation: Departamento de Urología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Igor
authors.initials: I
authors.lastname: Blaha
authors.affiliation: Departamento de Investigación, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Orensanz
authors.affiliation: Departamento de Urología, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Bustamante
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Prieto
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Medardo
authors.identifier: http://orcid.org/0000-0002-2960-9931
authors.initials: M
authors.lastname: Hernández
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D005260:Female; D007609:Kallidin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D043783:Receptor, Bradykinin B1 / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D013552:Swine; D014513:Ureter / Q000187:drug effects / Q000378:metabolism*; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D014665:Vasodilator Agents; D007609:Kallidin; D001920:Bradykinin
keywords: Ca2+ signaling; bradykinin receptors; inhibitory neurotransmission modulation; pig intravesical ureter; smooth muscle tension