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KMID : 1240020170210010020
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International Neurourology Journal
2017 Volume.21 No. 1 p.20 ~ p.28
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Ketanserin and Naftopidil Enhance the Potentiating Effect of Alpha-Methyl-Serotonin on the Neurally-Induced Contraction of Human Isolated Urinary Bladder Muscle Strips
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Hattori Tsuyoshi
Lluel Philippe
Rouget Celine
Rekik Moez
Yoshiyama Mitsuharu
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Abstract
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Purpose: The aim of this study was to assess the potential involvement of a specific subtype of 5-hydroxytryptamine (5-HT), 5HT2 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-HT2 receptor agonist, α-methyl-serotonin (α-Me-5-HT) (1nM?100μM) in the presence or absence of a 5-HT2 antagonist, ketanserin (5-HT2A>5-HT2C) or naftopidil (5-HT2B>5-HT2A) (0.3?3μM).
Results: 5-HT and α-Me-5-HT potentiated EFS-induced contraction with a maximal effect (Emax) of 37.6% and 38.6%, respectively, and with pEC50 (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 Emax 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 Emax 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-HT2 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.
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KEYWORD
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Serotonin Receptors, Alpha-1 Adrenergic Receptors, Urinary Bladder Neck Obstruction, Prostatism, Underactive Bladder
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