Contractile responses to natural tachykinins and selective tachykinin analogs in normal and inflamed ileal and colonic muscle.
Contractile responses to natural tachykinins and selective tachykinin analogs in normal and inflamed ileal and colonic muscle.
复制标题
正常和发炎的回肠和结肠肌肉对天然速激肽和选择性速激肽类似物的收缩反应。
DOI：
10.1080/003655201750153278
复制
发表时间：
2001
影响因子：
1.9
通讯作者：
P. Hellström
中科院分区：
文献类型：
--
作者：
A. Al;P. Hellström
背景
速激肽和乙酰胆碱是肠道内主要的生理性运动刺激剂，其作用途径是神经激肽和毒蕈碱受体。
方法
在器官浴中研究了正常回肠和结肠或炎症性肠病患者相应组织的纵向和环形肌条。收缩反应的速激肽物质P，神经激肽A，神经激肽B和神经肽γ和特定的类似物为各自的受体进行了比较，乙酰胆碱。
结果
乙酰胆碱可引起正常回肠和结肠纵肌和环肌的时相性收缩（均P < 0.01）。在炎症组织中，回肠收缩率降低至17%-33%（P < 0.05），结肠收缩率降低至3%-26%（P < 0.01）。天然速激肽及其特异性类似物均引起浓度依赖性的相位性、紧张性和节律性收缩（均P < 0.01）。神经肽γ在收缩回肠和结肠方面最有效，其次是神经激肽A、P物质和神经激肽B，更不用说神经肽γ和神经激肽A等效的回肠纵肌了。在速激肽类似物中，Nle 10-NKA（4-10）比P物质甲酯和senktide更有效，表明神经激肽2受体在速激肽的收缩作用中占主导地位。在炎症组织中，与对照组相比，回肠对速激肽的收缩反应降低至0%-42%（P < 0.05），结肠对速激肽的收缩反应降低至0%-17%（P < 0.01）。
结论
在人类中，速激肽主要通过激活神经激肽2受体发挥肠道收缩作用，其强度与乙酰胆碱相似。这些反应在溃疡性结肠炎和克罗恩病的炎症组织中大大降低。
BACKGROUND
Tachykinins and acetylcholine are main physiological motility stimulators in the gut by their effects exerted through neurokinin and muscarinic receptors.
METHODS
Longitudinal and circular muscle strips from normal ileum and colon or corresponding tissues from patients with inflammatory bowel disease were studied in organ baths. Contractile responses to the tachykinins substance P, neurokinin A, neurokinin B and neuropeptide gamma and specific analogs for their respective receptors were compared to acetylcholine.
RESULTS
Acetylcholine caused concentration-dependent phasic contractions in longitudinal and circular muscle of normal ileum and colon (both P < 0.01). In inflamed tissues, contractile responses were reduced to 17%-33% in ileum (P < 0.05) and 3%-26% in colon (P < 0.01). Both natural tachykinins and their specific analogs caused concentration-dependent phasic, tonic and rhythmic contractions (each P < 0.01). Neuropeptide gamma was most potent in contracting the ileum and colon, followed by neurokinin A, substance P and neurokinin B, let alone longitudinal muscle of the ileum where neuropeptide gamma and neurokinin A were equipotent. Of the tachykinin analogs, Nle10-NKA(4-10) was more potent than substance P methyl ester and senktide, indicating neurokinin 2 receptors are predominant for contractile effects of tachykinins. In inflamed tissues, contractile responses to tachykinins were reduced to 0%-42% in ileum (P < 0.05) and 0%-17% in colon (P < 0.01) compared to controls.
CONCLUSION
In humans, tachykinins exert gut contractile effects, of similar strength as acetylcholine, predominantly through activation of neurokinin 2 receptors. These responses are greatly reduced in inflamed tissues of ulcerative colitis and Crohn disease.