Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition-reflex pathway in the rat
Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition-reflex pathway in the rat
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DOI：
10.1152/ajpregu.2001.280.5.r1407
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发表时间：
2001-05-01
影响因子：
2.8
通讯作者：
De Groat, WC
中科院分区：
文献类型：
--
作者：
Kakizaki, H;Yoshiyama, M;De Groat, WC
5-中枢神经系统中的羟色胺（5-HT）受体与排尿控制有关。本研究旨在评价选择性5-HT 1A受体拮抗剂{N-[2-[4-（2-甲氧基苯基）-1-哌嗪基]乙基]-N-（2-吡啶基）环己烷甲酰胺三盐酸盐（WAY 100635）}对麻醉雌性Wistar大鼠排尿反射通路的影响。膀胱扩张引起的节律性等容膀胱收缩被取消0.3- 3毫克/公斤静脉注射或30- 100微克鞘内（IT）管理WAY 100635以剂量依赖的方式为3-15分钟。鞘内注射WAY 100635是有效的，只有当注射在L 6-S1脊髓水平，但不是在胸或颈髓水平。WAY 100635（30-100 μ g）显著降低了由脑桥排尿中枢的电刺激诱发的膀胱收缩的幅度。而鞘内或静脉注射WAY 100635均不影响电刺激盆神经诱发的脑桥头端场电位。这些结果表明，5-HT 1A受体在脊髓L 6-S1水平有一个重要的作用，在紧张性控制的下行分支的排尿反射途径在大鼠。
5-Hydroxytryptamine (5-HT) receptors in the central nervous system have been implicated in the control of micturition. The present study was undertaken to evaluate the effects of a selective 5-HT1A-receptor antagonist {N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY100635)} on the micturition-reflex pathway in urethane-anesthetized female Wistar rats. Rhythmic isovolumetric bladder contractions evoked by bladder distension were abolished by 0.3- to 3-mg/kg iv or 30- to 100-mug intrathecal (it) administration of WAY100635 in a dose-dependent manner for periods of 3-15 min. Intrathecal injection of WAY100635 was effective only if injected at the L6-S1 spinal cord level, but not at the thoracic or cervical cord levels. WAY100635 (30-100 mug it) significantly reduced the amplitude of bladder contractions evoked by electrical stimulation of the pontine micturition center. However, the field potentials in the rostral pons evoked by electrical stimulation of pelvic nerve were not affected by intrathecal or intravenous injection of WAY100635. These results suggest that 5-HT1A receptors at the L6-S1 level of the spinal cord have an important role in the tonic control of the descending limb of the micturition-reflex pathway in the rat.