Urological Research

, Volume 28, Issue 2, pp 116–121

Doxazosin modifies serotonin-mediated rabbit urinary bladder contraction

Potential clinical relevance
  • Masood A. Khan
  • Cecil S. Thompson
  • Mick R. Dashwood
  • Faiz H. Mumtaz
  • Dimitri P. Mikhailidis
  • Robert J. Morgan
ORIGINAL PAPER

DOI: 10.1007/s002400050148

Cite this article as:
Khan, M., Thompson, C., Dashwood, M. et al. Urological Research (2000) 28: 116. doi:10.1007/s002400050148

Abstract

5-Hydroxytryptamine (5-HT) induces rabbit detrusor contractions via 5-HT3 receptors. Similarly, 5-HT4 receptors are known to be present in the human bladder. Doxazosin, a non-selective α1 antagonist, is used for the symptomatic relief of bladder outflow obstruction. Previous work has shown that doxazosin inhibits 5-HT2-mediated platelet shape change. Hence, the aim of this study was to assess, using organ baths and autoradiography, whether doxazosin has any 5-HT-inhibiting activity in the rabbit detrusor. Detrusor strips from adult New Zealand White rabbits were placed in organ baths; phenoxybenzamine (10−5 M) was added to block alpha-receptors. After KCl responses were assessed, the tissues were exposed to 10−3 M 5-HT. Subsequently, the strips were incubated with doxazosin or ondansetron (10−5 M; 5-HT3 antagonist) followed by a further exposure to 5-HT. In some experiments, after the initial 5-HT-induced contractions, the tissues were washed and then re-exposed to 5-HT. These latter experiments acted as controls. Low-resolution autoradiography was performed on detrusor sections to assess the effect of doxazosin on 5-HT binding. These sections were analyzed densitometrically. Doxazosin and ondansetron produced a significant reduction in 5-HT-mediated contractions. Inhibition by doxazosin was in a concentration-dependent manner. Autoradiography demonstrated a significant reduction in [3H]-5-HT binding by doxazosin. Doxazosin significantly inhibits 5-HT-mediated contractions in the rabbit detrusor. This effect appears to be mainly mediated via 5-HT3 receptor inhibition. Autoradiographic evidence suggests that doxazosin reduces 5-HT binding in the rabbit detrusor. The beneficial effects of doxazosin in bladder outflow obstruction may be due, at least in part, to 5-HT antagonism.

Key words DoxazosinSerotoninRabbitUrinary bladder

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Masood A. Khan
    • 1
  • Cecil S. Thompson
    • 2
  • Mick R. Dashwood
    • 2
  • Faiz H. Mumtaz
    • 1
  • Dimitri P. Mikhailidis
    • 2
  • Robert J. Morgan
    • 1
  1. 1.Department of Urology, Royal Free and University College, Medical School (Royal Free Campus), University College LondonDE
  2. 2.Molecular Pathology and Clinical Biochemistry, Royal Free and University College, Medical School (Royal Free Campus), University College London, Pond Street, London NW3 2QG, UK Tel.: +44-171-7940500 ext 3481; Fax: +44-171-7949537GB