UROsphere, Faculté des Sciences Pharmaceutiques, 35 Chemin des Maraîchers, 31062 Toulouse cedex 09, France.
Eur J Pharmacol. 2011 Jan 10;650(1):403-10. doi: 10.1016/j.ejphar.2010.10.027. Epub 2010 Oct 20.
Serotonin (5-HT) enhances the neurogenic contractile response induced by electrical field stimulation (EFS) in the rat isolated urinary bladder. The aim of this study was to functionally characterize the receptors involved in this effect by using a range of 5-HT receptor subtype selective agonists and antagonists. 5-HT produced a concentration-dependent potentiation of contractile responses to EFS with a pEC(50) value of 6.86±0.24. SB-269970 (0.01, 0.1 and 1μM), a selective 5-HT(7) receptor antagonist, caused a concentration-dependent rightward shift of the 5-HT-induced response. The pA(2) value was 8.16 with a slope of 0.46±0.08. Neither ketanserine nor SB-204741, 5-HT(2A) and 5-HT(2B) receptors antagonists, respectively, affected the concentration-response curve to 5-HT. However, 5-HT response was antagonized by the selective 5-HT(2C) receptor antagonist SB-242084 (0.1 and 1μM). In the presence of 1μM of both antagonists SB-269970 and SB-242084, 5-HT response was almost fully inhibited. 5-CT, a 5-HT(7) receptor agonist, induced a biphasic concentration-dependent potentiation of neurogenic contractions. SB-269970 concentration-dependently antagonized the first phase of 5-CT response with a pA(2) value of 8.77 and a slope not significantly different from unity (0.91±0.11) that suggests a competitive antagonism. WAY-161503, a 5-HT(2C) receptor agonist (0.01-10μM), induced a concentration-dependent potentiation of contractile response to EFS while DOI (a selective 5-HT(2A) agonist) had no effect. SB-242084 (0.1 and 1μM) antagonized the effect of WAY-161503 in a concentration-dependent manner. The current results demonstrate that 5-HT potentiates neurogenic contractions of rat isolated detrusor muscle through both 5-HT(7) and 5-HT(2c) receptors.
血清素（5-HT）增强了大鼠离体膀胱中电刺激（EFS）诱导的神经源性收缩反应。本研究的目的是通过使用一系列 5-HT 受体亚型选择性激动剂和拮抗剂来对涉及该效应的受体进行功能表征。5-HT 对 EFS 诱导的收缩反应产生浓度依赖性增强作用，pEC50 值为 6.86±0.24。SB-269970（0.01、0.1 和 1μM），一种选择性 5-HT7 受体拮抗剂，导致 5-HT 诱导的反应发生浓度依赖性右移。pA2 值为 8.16，斜率为 0.46±0.08。无论是 ketanserine 还是 SB-204741，分别为 5-HT2A 和 5-HT2B 受体拮抗剂，都不影响 5-HT 的浓度-反应曲线。然而，选择性 5-HT2C 受体拮抗剂 SB-242084（0.1 和 1μM）拮抗 5-HT 反应。在 1μM 两种拮抗剂 SB-269970 和 SB-242084 的存在下，5-HT 反应几乎完全被抑制。5-CT，一种 5-HT7 受体激动剂，诱导神经源性收缩的双相浓度依赖性增强。SB-269970 浓度依赖性拮抗 5-CT 反应的第一相，pA2 值为 8.77，斜率与单位无显著差异（0.91±0.11），提示竞争性拮抗。WAY-161503，一种 5-HT2C 受体激动剂（0.01-10μM），诱导 EFS 诱导的收缩反应的浓度依赖性增强，而 DOI（一种选择性 5-HT2A 激动剂）没有作用。SB-242084（0.1 和 1μM）以浓度依赖性方式拮抗 WAY-161503 的作用。目前的结果表明，5-HT 通过 5-HT7 和 5-HT2c 受体增强大鼠离体逼尿肌的神经源性收缩。
