title: Ketanserin and Naftopidil Enhance the Potentiating Effect of Alpha-Methyl-Serotonin on the Neurally-Induced Contraction of Human Isolated Urinary Bladder Muscle Strips.
abstract: OBJECTIVE
  The aim of this study was to assess the potential involvement of a specific subtype of 5-hydroxytryptamine (5-HT), 5HT2receptors in neurally-induced contractions of the human detrusor.
  
  
  METHODS
  Contractile responses to electrical field stimulation (EFS) were examined in human isolated urinary bladder muscle strips. The potentiation of EFS-induced detrusor contraction was examined by adding cumulative concentrations of a 5-HT and 5-HT2receptor agonist, α-methyl-serotonin (α-Me-5-HT) (1nM-100μM) in the presence or absence of a 5-HT2antagonist, ketanserin (5-HT2A>5-HT2C) or naftopidil (5-HT2B>5-HT2A) (0.3-3μM).
  
  
  RESULTS
  5-HT and α-Me-5-HT potentiated EFS-induced contraction with a maximal effect (Emax) of 37.6% and 38.6%, respectively, and with pEC50(negative logarithm of the concentration required for a half-maximal response to an agonist) values of 8.3 and 6.8, respectively. Neither ketanserin nor naftopidil at any concentration produced a rightward displacement of the α-Me-5-HT concentration response curve. Instead, the Emaxof α-Me-5-HT increased in the presence of ketanserin at 0.3-1μM and in the presence of naftopidil at 1μM to 51% and 56%, respectively, while the Emaxin the presence of vehicle alone was 36%. The highest concentration (3μM) of either drug, however, fully reversed the enhancement.
  
  
  CONCLUSIONS
  The potentiating effect of α-Me-5-HT on neurally-induced contraction of human urinary bladder muscle strips was not found to be mediated via any 5-HT2receptor subtypes. The underlying mechanism for the enhancement of the α-Me-5-HT potentiating effect on detrusor contractility by ketanserin and naftopidil remains unknown; however, our results suggest that these drugs may be useful for treating contractile dysfunction of the detrusor, as manifested in conditions such as underactive bladder.
authors.affiliation: Department of Medical Affairs, Asahi Kasei Pharma Corporation, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.identifier: 0000-0001-6425-3945
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Department of Pharmacology, UROsphere SAS, Toulouse, France.
authors.forename: Philippe
authors.identifier: 0000-0002-7951-528X
authors.initials: P
authors.lastname: Lluel
authors.affiliation: Department of Pharmacology, UROsphere SAS, Toulouse, France.
authors.forename: Céline
authors.identifier: 0000-0002-4053-1151
authors.initials: C
authors.lastname: Rouget
authors.affiliation: Department of Pharmacology, UROsphere SAS, Toulouse, France.
authors.forename: Moèz
authors.identifier: 0000-0001-6132-7064
authors.initials: M
authors.lastname: Rekik
authors.affiliation: Department of Urology, University of Yamanashi Graduate School of Medical Science, Chuo, Yamanashi, Japan.
authors.forename: Mitsuharu
authors.identifier: 0000-0001-8695-884X
authors.initials: M
authors.lastname: Yoshiyama
keywords: Alpha-1 Adrenergic Receptors; Prostatism; Serotonin Receptors; Underactive Bladder; Urinary Bladder Neck Obstruction