title: Involvement of connexins 43 and 45 in functional mechanism of human detrusor overactivity in neurogenic bladder.
abstract: OBJECTIVE
  To assess the involvement of connexins (Cxs) 43 and 45 in the selective inhibition of detrusor contractions in patients with neurogenic detrusor overactivity (NDO).
  
  
  METHODS
  Detrusor strips with and without mucosa were obtained from patients undergoing cystectomy for either neurogenic bladder with NDO refractory to pharmacologic treatment or bladder cancer with no overactive bladder symptoms (ie, control group). The strips were isometrically mounted in organ baths. The effects of the selective inhibitors Cxs 43 and 45 on carbachol-induced contractions of bladder strips were assessed.
  
  
  RESULTS
  Overall, 47 patients with a median age of 61 years (range 19-83) were included. The female-to-male ratio was 0.42. Selective inhibitors of Cxs 43 and 45 significantly inhibited carbachol-induced contractions of bladder strips from patient with NDO (P <.01) but had no effect in the control group. When tested without mucosa, the effect of the Cx 43 inhibitor in the NDO patient strips was abolished, but it remained unchanged with the Cx 45 inhibitor (P <.05).
  
  
  CONCLUSIONS
  The pharmacologic modulation of Cx-mediated intercellular communication, targeting Cxs 43 and 45, is directly involved in the functional mechanism of NDO and might represent a future target for the treatment of NDO.
authors.affiliation: Department of Urology, AP-HP, Pitié-Salpêtrière Academic Hospital, Pierre et Marie Curie Medical School, Paris VI University, Paris, France. veronique.phe@psl.aphp.fr
authors.forename: Véronique
authors.initials: V
authors.lastname: Phé
authors.forename: Delphine
authors.initials: D
authors.lastname: Behr-Roussel
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Oger-Roussel
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chartier-Kastler
authors.forename: Thierry
authors.initials: T
authors.lastname: Lebret
authors.forename: Gilles
authors.initials: G
authors.lastname: Karsenty
authors.forename: Eva
authors.initials: E
authors.lastname: Compérat
authors.forename: Philippe
authors.initials: P
authors.lastname: Camparo
authors.forename: François
authors.initials: F
authors.lastname: Giuliano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology*; D001750:Urinary Bladder, Neurogenic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D018031:Connexin 43; D017630:Connexins; C082920:connexin 45