8.
INTRODUCTION: The purpose of this study is to investigate in vitro the effects of serotonin on the rat detrusor. In particular, it examines which drugs inhibit the serotonin-induced detrusor contractions. MATERIALS AND METHODS: Isometric tension changes of isolated rat bladder muscle strips were recorded in an organ bath using a force transducer. Acute effects of serotonin (0.0001-0.01 mM) on resting tension were assessed. Electrical field stimulation (EFS); bethanechol (0.0001-0.01 mM); ATP (1-3 mM)- or KCl (63.5-254 mM)-induced contractions using an application in an organ bath were compared with serotonin-induced contractions. In order to examine the action mechanism of serotonin-induced stimulation, EFS-, bethanechol-, ATP- or KCl-induced contraction on serotonin treatment (0.001 mM) was assessed and serotonin (0.001-0.1 mM) was cumulatively added to the organ bath following preincubation with propranolol, ketanserin, tropisetron, propiverine, sodium nitroprusside or doxazosin. RESULTS: The serotonin-induced response has two phases: an initial transient contraction and a prolonged tonic phase. Serotonin produced a reversible and dose-dependent contraction of the detrusor strips. Responses to bethanechol significantly increased with a concentration of 0.001 mM serotonin (p < 0.05). There was no effect on the responses to ATP, KCl, or EFS on 0.001 mM serotonin. The 5-HT(2) receptor is mainly responsible for serotonin-induced contractions of the detrusor (p < 0.05), while the 5-HT(1) receptor is partially responsible. Doxazosin and propiverine each significantly suppressed the response to serotonin, while sodium nitroprusside and tropisetron each had no effect (p < 0.05). CONCLUSIONS: Because the 5-HT(2) antagonist blocked the effect of serotonin-induced bladder contractions and the stimulation of the adrenoreceptors, the 5-HT(2) antagonist seems to improve lower urinary tract symptoms.
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