title: Mucosa of murine detrusor impairs β2 -adrenoceptor-mediated relaxation.
abstract: OBJECTIVE
  To investigate the role of the mucosa in (-)-isoprenaline-induced relaxation of mouse detrusor muscle and to characterize the β-adrenoceptor subtypes involved.
  
  
  METHODS
  Isolated intact and mucosa-denuded muscle strips from the urinary bladder of male C57BL6 mice were pre-contracted with KCl (40 mM) and were relaxed with increasing concentrations of the β-adrenoceptor (β-AR) agonist (-)-isoprenaline and forskolin in the presence and absence of the subtype-selective β-AR blockers CGP20712A (β1 -ARs), ICI118,551 (β2 -ARs), and L748,337 (β3 -ARs).
  
  
  RESULTS
  Force development in response to KCl was larger in mucosa-denuded than in intact preparations and was almost completely relaxed with increasing concentrations of (-)-isoprenaline. Mucosa-denuded muscles were about 10-fold more sensitive to (-)-isoprenaline than intact muscles. CGP20712A did not affect the concentration-response curves (CRCs) to (-)-isoprenaline, ICI118,551 shifted the CRC further to the right in denuded than in intact strips so that the difference between them was abolished. Combined exposure to β1 -AR and β2 -AR blocker yielded the same result. L748,337 did not significantly affect the CRC to (-)-isoprenaline but caused additional blockade to ICI118,551 in the presence of intact mucosa.
  
  
  CONCLUSIONS
  The mucosa of mouse detrusor strips impairs KCl-induced force development and reduces the sensitivity to β-AR-induced relaxation. The relaxing response to (-)-isoprenaline as well as the mucosa effect thereupon are mainly mediated by β2 -ARs. A minor involvement of β3 -ARs becomes apparent particularly at high (-)-isoprenaline concentrations.
authors.affiliation: Department of Pharmacology and Toxicology, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|Department of Urology, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Propping
authors.affiliation: Department of Pharmacology and Toxicology, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Manja
authors.initials: M
authors.lastname: Newe
authors.affiliation: Department of Pharmacology, University of Murcia, Murcia, Spain.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Kaumann
authors.affiliation: Department of Urology, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Manfred P
authors.initials: MP
authors.lastname: Wirth
authors.affiliation: Department of Pharmacology and Toxicology, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Ravens
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000627:Aminophenols; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D013449:Sulfonamides; D001743:Urinary Bladder / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D000627:Aminophenols; D007093:Imidazoles; C120576:L 748,337; D013449:Sulfonamides; D014665:Vasodilator Agents; D005576:Colforsin; D011189:Potassium Chloride; C049763:CGP 20712A; D007545:Isoproterenol
keywords: detrusor smooth muscle; mucosa; relaxation; urothelium; β-adrenoceptors