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Doxazosin modifies serotonin-mediated rabbit urinary bladder contraction. Potential clinical relevance
M A Khan1, C S Thompson, M R Dashwood
1Department of Urology, Royal Free and University College, Medical School, University College, London.
Urological Research
|June 13, 2000
Summary
Doxazosin significantly reduces 5-hydroxytryptamine (5-HT)-mediated rabbit detrusor contractions, primarily through 5-HT3 receptor inhibition. This study suggests a novel mechanism for doxazosin
Area of Science:
- Pharmacology
- Urology
Background:
- 5-Hydroxytryptamine (5-HT) induces rabbit detrusor contractions via 5-HT3 receptors.
- 5-HT4 receptors are present in the human bladder.
- Doxazosin, an alpha1 antagonist, treats bladder outflow obstruction symptoms.
Purpose of the Study:
- To assess doxazosin's 5-HT-inhibiting activity in the rabbit detrusor.
- Investigate the mechanism of doxazosin's action on detrusor smooth muscle.
- Evaluate doxazosin's potential role in bladder outflow obstruction treatment.
Main Methods:
- Organ bath studies with rabbit detrusor strips, with alpha-receptors blocked.
- Assessment of 5-HT-induced contractions after incubation with doxazosin or ondansetron (5-HT3 antagonist).
- Low-resolution autoradiography to analyze doxazosin's effect on [3H]-5-HT binding in detrusor sections.
Main Results:
- Doxazosin and ondansetron significantly reduced 5-HT-mediated detrusor contractions.
- Doxazosin's inhibitory effect was concentration-dependent.
- Autoradiography showed doxazosin significantly reduced [3H]-5-HT binding.
Conclusions:
- Doxazosin significantly inhibits 5-HT-mediated contractions in the rabbit detrusor.
- The primary mechanism appears to be 5-HT3 receptor antagonism.
- Doxazosin's benefits in bladder outflow obstruction may involve 5-HT antagonism.