Intrathecally administered substance P activated the spinal defecation center and enhanced colorectal motility in anesthetized rats
Intrathecally administered substance P activated the spinal defecation center and enhanced colorectal motility in anesthetized rats
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DOI：
10.1152/ajpgi.00342.2021
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发表时间：
2022-07-01
影响因子：
4.5
通讯作者：
Shimizu，Yasutake
中科院分区：
文献类型：
--
作者：
Naitou，Kiyotada;Iwashita，Honoka;Shimizu，Yasutake
对结直肠的伤害性刺激通过激活从脊髓上排便中心投射到脊髓排便中心的下行单胺能通路引起结直肠收缩。由于已知P物质参与脊髓对外周伤害性刺激的反应，我们研究了在L 6-S1水平鞘内注射P物质对用α-氯醛糖和氯胺酮麻醉的大鼠结肠直肠运动的影响。鞘内注射P物质增强结直肠运动，即使在T4水平横断胸脊髓后。切断盆腔神经，但不是结肠神经，取消P物质增强大肠运动。RT-PCR检测脊髓L 6-S1节段神经激肽（NK）1-3受体mRNA的表达。免疫组化结果显示，盆神经节前神经元表达NK 1受体，而不表达NK 2受体，在表达NK 1受体的神经元周围有密集的含P物质的纤维支配。鞘内给药的NK 1受体拮抗剂（spantide）衰减辣椒素诱导的结直肠收缩。这些结果表明，在脊髓排便中枢的NK 1受体介导的P物质的结肠动力学行动。我们的研究结果表明，P物质可能作为一种神经递质在脊髓排便center.NEW &值得注意的是，我们发现，鞘内注射P物质增强麻醉大鼠的结肠直肠运动。神经激肽（NK）1受体，但没有NK 2受体，检测到节前神经元的盆神经。阻断脊髓中的NK 1受体可减弱结肠内伤害性刺激引起的结肠动力增强。研究结果表明，P物质可能作为一种神经递质的脊髓反射通路控制排便。
Noxious stimuli on the colorectum cause colorectal contractions through activation of descending monoaminergic pathways projecting from the supraspinal defecation center to the spinal defecation center. Since it is known that substance P is involved in the response to peripheral noxious stimuli in the spinal cord, we investigated the effects of intrathecally administered substance P at L6–S1 levels on colorectal motility in rats that were anesthetized with α-chloralose and ketamine. Intrathecally administered substance P enhanced colorectal motility, even after transection of the thoracic spinal cord at the T4 level. Severing the pelvic nerves, but not the colonic nerves, abolished substance P enhanced colorectal motility. In the spinal cord at L6–S1 levels, expression of mRNA coding neurokinin (NK) 1–3 receptors was detected by RT-PCR. Immunohistological experiments revealed that preganglionic neurons of the pelvic nerves express NK1 receptors, whereas expression of NK2 receptors was not found. In addition, substance P-containing fibers densely innervated around the preganglionic neurons expressing NK1 receptors. An intrathecally administered NK1 receptor antagonist (spantide) attenuated capsaicin-induced colorectal contractions. These results suggest that the colokinetic action of substance P is mediated by the NK1 receptor in the spinal defecation center. Our findings indicate that substance P may function as a neurotransmitter in the spinal defecation center.NEW & NOTEWORTHYWe found that intrathecally administered substance P enhanced colorectal motility in anesthetized rats. Neurokinin (NK) 1 receptors, but not NK2 receptors, were detected in preganglionic neurons of the pelvic nerves. Blockade of NK1 receptors in the spinal cord attenuated the enhanced colorectal motility in response to intracolonic noxious stimuli. The findings indicate that substance P may function as a neurotransmitter in the spinal reflex pathway controlling defecation.