Medullary raphe nuclei activate the lumbosacral defecation center through the descending serotonergic pathway to regulate colorectal motility in rats.
Medullary raphe nuclei activate the lumbosacral defecation center through the descending serotonergic pathway to regulate colorectal motility in rats.
复制标题
中缝髓核通过下降的血清素能通路激活腰骶排便中枢，调节大鼠结直肠运动。
DOI：
10.1152/ajpgi.00317.2017
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Shimizu Y.
中科院分区：
文献类型：
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作者：
Nakamori H;Naitou K;Horii Y;Shimaoka H;Horii K;Sakai H;Yamada A;Furue H;Shiina T;Shimizu Y.
结直肠运动由位于大脑和脊髓的两个排便中心调节。在之前的研究中，我们已经表明，在腰骶脊髓中施用血清素（5-HT）会导致结直肠运动增强。由于脊髓 5-HT 来源于中缝髓核的神经元，包括中缝大核、中缝暗核和中缝苍白核，因此我们检查了中缝髓核的刺激是否通过腰骶排便中枢增强结直肠运动。用气球记录麻醉大鼠体内的结直肠压力。中缝髓核的电刺激未能增强结直肠运动。由于中缝刺激可以同时激活 GABA 能神经元，并释放 GABA 掩模，加速中缝核对腰骶排便中枢的作用，因此预先鞘内注射 GABAA 受体拮抗剂以表现出兴奋反应。当脊髓 GABAA 受体被拮抗剂阻断时，中缝髓核的电刺激会增加结直肠收缩。鞘内注射 2 型 5-羟色胺 (5-HT2) 和 3 型 (5-HT3) 受体拮抗剂可抑制中缝核的这种作用。此外，在腰骶脊髓中注射选择性 5-HT 再摄取抑制剂可增强中缝刺激引起的结直肠运动增强。盆腔神经的横断，但结肠神经的横断，阻止了中缝核对结直肠运动的影响。这些结果表明，中缝髓核的激活通过腰骶排便中心的 5-HT2 和 5-HT3 受体引起结直肠的增强收缩。新的和值得注意的我们已经表明，中缝髓核的电刺激通过大鼠的盆腔神经引起结直肠的增强收缩。中缝髓核对结直肠运动的影响是通过激活腰骶排便中枢的 5-羟色胺 2 型和 3 型受体来发挥的。下降的血清素能中缝脊髓束代表了针对肠易激综合征等结直肠运动障碍的新的潜在治疗靶点。
Colorectal motility is regulated by two defecation centers located in the brain and spinal cord. In previous studies, we have shown that administration of serotonin (5-HT) in the lumbosacral spinal cord causes enhancement of colorectal motility. Because spinal 5-HT is derived from neurons of the medullary raphe nuclei, including the raphe magnus, raphe obscurus, and raphe pallidus, we examined whether stimulation of the medullary raphe nuclei enhances colorectal motility via the lumbosacral defecation center. Colorectal pressure was recorded with a balloon in vivo in anesthetized rats. Electrical stimulation of the medullary raphe nuclei failed to enhance colorectal motility. Because GABAergic neurons can be simultaneously activated by the raphe stimulation and released GABA masks accelerating actions of the raphe nuclei on the lumbosacral defecation center, a GABAAreceptor antagonist was preinjected intrathecally to manifest excitatory responses. When spinal GABAAreceptors were blocked by the antagonist, electrical stimulation of the medullary raphe nuclei increased colorectal contractions. This effect of the raphe nuclei was inhibited by intrathecal injection of 5-hydroxytryptamine type 2 (5-HT2) and type 3 (5-HT3) receptor antagonists. In addition, injection of a selective 5-HT reuptake inhibitor in the lumbosacral spinal cord augmented the raphe stimulation-induced enhancement of colorectal motility. Transection of the pelvic nerves, but not transection of the colonic nerves, prevented the effect of the raphe nuclei on colorectal motility. These results demonstrate that activation of the medullary raphe nuclei causes augmented contractions of the colorectum via 5-HT2and 5-HT3receptors in the lumbosacral defecation center.NEW & NOTEWORTHYWe have shown that electrical stimulation of the medullary raphe nuclei causes augmented contractions of the colorectum via pelvic nerves in rats. The effect of the medullary raphe nuclei on colorectal motility is exerted through activation of 5-hydroxytryptamine type 2 and type 3 receptors in the lumbosacral defecation center. The descending serotoninergic raphespinal tract represents new potential therapeutic targets against colorectal dysmotility such as irritable bowel syndrome.