A 5-HT4 agonist, mosapride, enhances intrinsic rectorectal and rectoanal reflexes after removal of extrinsic nerves in guinea pigs
A 5-HT4 agonist, mosapride, enhances intrinsic rectorectal and rectoanal reflexes after removal of extrinsic nerves in guinea pigs
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DOI：
10.1152/ajpgi.00532.2004
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发表时间：
2005-08-01
影响因子：
4.5
通讯作者：
Takaki, M
中科院分区：
文献类型：
--
作者：
Kojima, Y;Nakagawa, T;Takaki, M
5-HT4激动剂莫沙必利可增强豚鼠切除外源性神经后的直肠和直肠肛门反射。Am J Physiol胃肠病肝生理学289：G351-G360,2005。2005年4月7日首次出版；DOI：10.1152/ajpgi.00532.2004。-在豚鼠中，直肠(R-R)收缩和直肠内括约肌(R-IAS)松弛的膨胀诱发反射可以通过外在的骶部兴奋性神经通路(骨盆神经)以及内在的胆碱能兴奋性和氮能抑制通路产生。本研究的目的是通过挤压(破坏腰椎和骶髓)建立固有的R-R和R-IAS反射模型，并评价5-HT4受体激动剂苯胺莫沙必利是否增强这些反射。记录麻醉豚鼠髓后第2~9天R-R和R-IAS的机械活动。尽管髓后扩张时的直肠基础压显著低于对照组，但髓后4~9d的R-R收缩反射指数和R-IAS同步松弛反射指数无明显变化。自发性直肠运动频率和IAS也没有变化。免疫组织化学研究显示髓后Cajal肌间和肌内间质细胞(ICC)的分布没有改变。莫沙必利(0.1-1.0 mg/kg，iv)可剂量依赖性地增加R-R(最大值：1.82)和R-IAS反射指数(最大值：2.76)。5-羟色胺受体拮抗剂GR-113808(1.0 mg/kg iv)使R-R和R-iAS反射指数降低约50%，并可拮抗莫沙必利的作用。结果表明，莫沙必利适度增强内源性R-R和R-IAS反射，可通过内源性激活的内源性5-HT4受体实现外源性神经剥夺后的功能性代偿。
A 5-HT4 agonist, mosapride, enhances intrinsic rectorectal and rectoanal reflexes after removal of extrinsic nerves in guinea pigs. Am J Physiol Gastrointest Liver Physiol 289: G351-G360, 2005. First published April 7, 2005; doi:10.1152/ajpgi.00532.2004.-Distension- evoked reflex of rectorectal (R-R) contractions and rectointernal anal sphincter (R-IAS) relaxations can be generated in guinea pigs through an extrinsic sacral excitatory neural pathway (pelvic nerves) as well as intrinsic cholinergic excitatory and nitrergic inhibitory pathways. The aim of the present study was to create intrinsic R-R and R-IAS reflex models by pithing (destruction of the lumbar and sacral cords; PITH) and to evaluate whether the prokinetic benzamide mosapride, a 5-HT4 receptor agonist, enhances these reflexes. The mechanical activities of the R-R and R-IAS were recorded in the anesthetized guinea pig on days 2-9 after PITH. Although the basal rectal pressure at distension after PITH was significantly lower than control, the reflex indexes of R-R contractions and synchronous R-IAS relaxations were unchanged between days 4 and 9 after PITH. The frequency of spontaneous rectal and IAS motility were also unchanged. Immunohistochemical studies revealed that the distribution of myenteric and intramuscular interstitial cells of Cajal (ICC) were not altered after PITH. Mosapride (0.1-1.0 mg/kg iv) dose-dependently increased both intrinsic R-R ( maximum: 1.82) and R-IAS reflex indexes (maximum: 2.76) from control (1.0) 6 - 9 days after PITH. The 5-HT4 receptor antagonist, GR-113808 ( 1.0 mg/kg iv) decreased the R-R and R-IAS reflex indexes by similar to 50% and antagonized the effect of mosapride (1.0 mg/kg iv). The present results indicate that mosapride moderately enhanced intrinsic R-R and R-IAS reflexes functionally compensated after deprivation of extrinsic nerves, mediated through endogenously active intrinsic 5-HT4 receptors.