title: Pharmacological Modulation of Mucosa-Related Impairment of β-Adrenoceptor-Mediated Relaxation in Human Detrusor.
abstract: OBJECTIVE
  The mucosa of human detrusor strips impairs catecholamine-induced relaxation. In order to elucidate which signal transduction pathways are involved in this cross talk between the mucosa and detrusor, we have studied the effects of several pharmacological agonists and antagonists on noradrenaline-mediated relaxation in intact and mucosa-denuded detrusor strips.
  
  
  METHODS
  Strips of detrusor tissue were obtained from patients who had undergone cystectomy for bladder cancer and were set up for force measurement. KCl- or carbachol-precontracted strips were relaxed with increasing concentrations of noradrenaline in the absence and in the presence of nitric oxide synthase inhibitor, L-NAME; P2X-receptor antagonist, PPADS; ETA-receptor antagonist, BQ-123; ETB-receptor antagonist, BQ-788; cyclooxygenase inhibitor, diclofenac; AT1-receptor antagonist, candesartan; and NK1-receptor antagonist, L-703,606.
  
  
  RESULTS
  In intact strips, KCl-stimulated force was enhanced by all blockers; carbachol-stimulated force increased with L-703,606. In denuded strips, only L-NAME augmented the KCl-stimulated contraction. Noradrenaline relaxed the precontracted detrusor strips to a significantly larger extent and at lower concentrations in denuded than in intact strips. L-NAME, PPADS and BQ-123/BQ-788 had little effect on noradrenaline-induced relaxation, whereas diclofenac, candesartan and L-703,606 sensitized intact carbachol-stimulated detrusor strips to noradrenaline-induced relaxation.
  
  
  CONCLUSIONS
  Inhibition of the noradrenaline-induced relaxation of precontracted human detrusor strips by the mucosa is attenuated by diclofenac, candesartan and L-703,606 suggesting the involvement of prostanoids, angiotensin and neurokinin pathways. Further experiments are required to unravel the exact mechanisms.
authors.affiliation: Institute of Pharmacology and Toxicology, Medizinische Fakultx00E4;t Carl Gustav Carus, Technische Universitx00E4;t Dresden, Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Propping
authors.forename: Melanie
authors.initials: M
authors.lastname: Roedel
authors.forename: Manfred P
authors.initials: MP
authors.lastname: Wirth
authors.forename: Ursula
authors.initials: U
authors.lastname: Ravens
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D009638:Norepinephrine / Q000819:agonists* / Q000037:antagonists & inhibitors*; D011943:Receptors, Adrenergic, beta; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology*; D019459:Urothelium / Q000187:drug effects / Q000502:physiology
chemical_list: D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine