Int Neurourol J.  2017 Mar;21(1):20-28. 10.5213/inj.1732758.379.

Ketanserin and Naftopidil Enhance the Potentiating Effect of Alpha-Methyl-Serotonin on the Neurally-Induced Contraction of Human Isolated Urinary Bladder Muscle Strips

Affiliations
  • 1Department of Medical Affairs, Asahi Kasei Pharma Corporation, Tokyo, Japan. hattori.tg@om.asahi-kasei.co.jp
  • 2Department of Pharmacology, UROsphere SAS, Toulouse, France.
  • 3Department of Urology, University of Yamanashi Graduate School of Medical Science, Chuo, Yamanashi, Japan.

Abstract

PURPOSE
The aim of this study was to assess the potential involvement of a specific subtype of 5-hydroxytryptamine (5-HT), 5HT(2) receptors 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-HT(2) receptor agonist, α-methyl-serotonin (α-Me-5-HT) (1nM-100μM) in the presence or absence of a 5-HT₂ antagonist, ketanserin (5-HT(2A)>5-HT(2C)) or naftopidil (5-HT(2B)>5-HT(2A)) (0.3-3μM).
RESULTS
5-HT and α-Me-5-HT potentiated EFS-induced contraction with a maximal effect (E(max)) of 37.6% and 38.6%, respectively, and with pEC(50) (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 E(max) of 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 E(max) in 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-HT(2) receptor 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.

Keyword

Serotonin Receptors; Alpha-1 Adrenergic Receptors; Urinary Bladder Neck Obstruction; Prostatism; Underactive Bladder

MeSH Terms

Humans*
Ketanserin*
Prostatism
Receptors, Adrenergic, alpha-1
Receptors, Serotonin
Serotonin
Urinary Bladder Neck Obstruction
Urinary Bladder*
Ketanserin
Receptors, Adrenergic, alpha-1
Receptors, Serotonin
Serotonin
Full Text Links
  • INJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr