title: β-Adrenoceptor-Mediated Relaxation of Carbachol-Pre-Contracted Mouse Detrusor.
abstract: OBJECTIVE
  To study the β-adrenoceptor subtypes involved in the relaxation responses to (-)-isoprenaline in carbachol-pre-contracted (CCh) mouse detrusor muscle with intact and denuded mucosa.
  
  
  METHODS
  Isolated muscle strips from the urinary bladder of male C57BL6 mice or β2-adrenoceptor knockout mice were pre-contracted with CCh, 1 µM and relaxed with increasing concentrations of the β-adrenoceptor (β-AR) agonist (-)-isoprenaline and forskolin. For estimating the β-AR subtypes involved, subtype-selective receptor blockers were used, that is, CGP 20712A (β1-ARs), ICI 118,551 (β2-ARs), and L748,337 (β3-ARs).
  
  
  RESULTS
  Unlike in KCl-pre-contracted muscle, the mucosa did not affect the sensitivity of the relaxation response to (-)-isoprenaline in CCh-pre-contracted murine detrusor strips. Increasing concentrations of (-)-isoprenaline produced a biphasic concentration-relaxation response without any difference both during the presence and absence of mucosa. The relaxation fraction produced by low (-)-isoprenaline concentrations was mediated by β2-AR as evidenced by a shift of the concentration-response curve to higher concentrations with ICI 118,551, but not with CGP 20712A and L748,337, and by the absence of this fraction in β2-AR-KO mice. The relaxation response with low sensitivity to (-)-isoprenaline was not affected by any of the β-AR subtype-selective blockers and was the only response detected in detrusor strips from β2-AR-KO mice.
  
  
  CONCLUSIONS
  In CCh-pre-contracted mouse detrusor, β2-ARs are responsible for the relaxation component with high sensitivity to (-)-isoprenaline as indicated by the conversion of a biphasic into a monophasic CRC with ICI 118,551 or by its absence in β2-AR KO mice. The mucosa does not impair relaxation under these conditions.
authors: Institute of Pharmacology and Toxicology, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors: Stefan
authors: S
authors: Propping
authors: Manja
authors: M
authors: Newe
authors: Kristina
authors: K
authors: Lorenz
authors: Manfred P
authors: MP
authors: Wirth
authors: Ursula
authors: U
authors: Ravens
mesh_terms: D000627:Aminophenols / Q000737:chemistry; D000818:Animals; D002217:Carbachol / Q000737:chemistry*; D018679:Cholinergic Agonists / Q000737:chemistry; D005576:Colforsin / Q000737:chemistry; D006720:Homozygote; D007093:Imidazoles / Q000737:chemistry; D007545:Isoproterenol / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000473:pathology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000473:pathology*; D011412:Propanolamines / Q000737:chemistry; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D013449:Sulfonamides / Q000737:chemistry; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000627:Aminophenols; D018679:Cholinergic Agonists; D007093:Imidazoles; C120576:L 748,337; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D018343:Receptors, Adrenergic, beta-2; D013449:Sulfonamides; D005576:Colforsin; C026777:ICI 118551; D002217:Carbachol; C049763:CGP 20712A; D007545:Isoproterenol