Chang F Y, Lee S D, Yeh G H, Wang P S
Division of Gastroenterology, Veterans General Hospital-Taipei, Taiwan, Republic of China.
J Gastroenterol Hepatol. 1999 Jan;14(1):39-45. doi: 10.1046/j.1440-1746.1999.01808.x.
Natural neurokinins (NK) and their specific receptor agonists, including substance P (SP), neurokinin A (NKA), neurokinin B (NKB), septide, [NIe10]-NKA4-10 and senktide, were used to assess whether they could activate established NK receptors in rat gastrointestinal tract and central nervous system to alter gastric emptying or intestinal transit. Fasting rats were intubated with an orogastric catheter to feed them liquid radiochromium. Neurokinins and analogues (at 10(-10), 10(-9), 10(-8) and 10(-7) mol/kg) and vehicle (saline + 0.1% bovine serum albumin) were injected via an intraperitoneal route. Rats were killed 15 min later and the whole gut was removed. The radioactivity of the stomach and 10 equally divided small intestinal segments was counted to determine gastric emptying and the geometric centre of intestinal transit. Septide treatment at 10(-8) and 10(-7) mol/kg markedly delayed gastric emptying. All doses of NKA inhibited gastric emptying. However, other peptides did not influence gastric emptying. Both septide and NKB treatment at 10(-8) and 10(-7) mol/kg enhanced intestinal transit. Substance P or senktide treatment (10-(-7) mol/kg) also enhanced intestinal transit. Stasis of remaining radioactivity in the proximal intestine was found following SP, septide, NKA and NKB treatment, whereas accelerated transit in the distal intestine was induced following NKA, NKB and senktide treatment. In conclusion, the in vivo study of NK and their specific agonists manifests a selective influence of these compounds on rat gastrointestinal tract. This selective activation of stomach NK1 and NK2 receptors delays gastric emptying, whereas activation of intestinal NK1 and NK3 receptors enhances intestinal transit.
天然神经激肽（NK）及其特异性受体激动剂，包括P物质（SP）、神经激肽A（NKA）、神经激肽B（NKB）、七肽、[Nle10]-NKA4-10和速激肽，用于评估它们是否能激活大鼠胃肠道和中枢神经系统中已确立的NK受体，从而改变胃排空或肠道转运。禁食大鼠经口胃导管插管，给它们喂食液体放射性铬。神经激肽及其类似物（浓度为10^(-10)、10^(-9)、10^(-8)和10^(-7) mol/kg）以及赋形剂（生理盐水+0.1%牛血清白蛋白）通过腹腔内途径注射。15分钟后处死大鼠，取出整个肠道。对胃和10个等长的小肠段进行放射性计数，以确定胃排空和肠道转运的几何中心。10^(-8)和10^(-7) mol/kg剂量的七肽处理显著延迟胃排空。所有剂量的NKA均抑制胃排空。然而，其他肽对胃排空没有影响。10^(-8)和10^(-7) mol/kg剂量的七肽和NKB处理均增强肠道转运。P物质或速激肽处理（10^(-7) mol/kg）也增强肠道转运。SP、七肽、NKA和NKB处理后，近端肠道中剩余放射性物质出现停滞，而NKA、NKB和速激肽处理后，远端肠道出现转运加速。总之，对NK及其特异性激动剂的体内研究表明，这些化合物对大鼠胃肠道有选择性影响。胃NK1和NK2受体的这种选择性激活会延迟胃排空，而肠道NK1和NK3受体的激活则会增强肠道转运。
