caa a22 4500 475743024 CHVBK 20180406123505.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1007/s002400050148 doi (NATIONALLICENCE)springer-10.1007/s002400050148 Doxazosin modifies serotonin-mediated rabbit urinary bladder contraction [Elektronische Daten] Potential clinical relevance [Masood A. Khan, Cecil S. Thompson, Mick R. Dashwood, Faiz H. Mumtaz, Dimitri P. Mikhailidis, Robert J. Morgan] 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. Springer-Verlag Berlin Heidelberg, 2000 Key words Doxazosin nationallicence Serotonin nationallicence Rabbit nationallicence Urinary bladder nationallicence Khan Masood A. Department of Urology, Royal Free and University College, Medical School (Royal Free Campus), University College London, DE aut Thompson Cecil S. 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: +44-171-7949537, GB aut Dashwood Mick R. 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: +44-171-7949537, GB aut Mumtaz Faiz H. Department of Urology, Royal Free and University College, Medical School (Royal Free Campus), University College London, DE aut Mikhailidis Dimitri P. 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: +44-171-7949537, GB aut Morgan Robert J. Department of Urology, Royal Free and University College, Medical School (Royal Free Campus), University College London, DE aut https://doi.org/10.1007/s002400050148 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002400050148 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Khan Masood A. Department of Urology, Royal Free and University College, Medical School (Royal Free Campus), University College London, DE aut NATIONALLICENCE 700 1- Thompson Cecil S. 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: +44-171-7949537, GB aut NATIONALLICENCE 700 1- Dashwood Mick R. 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: +44-171-7949537, GB aut NATIONALLICENCE 700 1- Mumtaz Faiz H. Department of Urology, Royal Free and University College, Medical School (Royal Free Campus), University College London, DE aut NATIONALLICENCE 700 1- Mikhailidis Dimitri P. 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: +44-171-7949537, GB aut NATIONALLICENCE 700 1- Morgan Robert J. Department of Urology, Royal Free and University College, Medical School (Royal Free Campus), University College London, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer