速激肽在体外通过NK2受体使人体食管体部的环形肌收缩。

Tachykinins contract the circular muscle of the human esophageal body in vitro via NK2 receptors.

作者信息

Huber O, Bertrand C, Bunnett N W, Pellegrini C A, Nadel J A, Debas H T, Geppetti P

机构信息

Department of Surgery, University of California, San Francisco.

出版信息

Gastroenterology. 1993 Oct;105(4):981-7. doi: 10.1016/0016-5085(93)90940-e.

DOI:10.1016/0016-5085(93)90940-e

PMID:7691676

Abstract

BACKGROUND

The action of tachykinins in the circular muscle of the human esophageal body is not known. The present study aimed to determine the response to tachykinins and the receptor type mediating this response.

METHODS

Specimen were obtained from organ donors or patients undergoing esophagectomy for cancer, and isometric tension in response to tachykinins was measured.

RESULTS

Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) evoked a concentration-dependent contraction with the following order of potency: NKA > NKB > SP. The neutral endopeptidase inhibitor, phosphoramidon, increased only the response to SP. [beta Ala8]NKA(4-10), a selective agonist of the NK2 receptor, produced a concentration-dependent contraction, whereas [Sar9,Met(O2)11]SP and [MePhe7]NKB, selective agonists of NK1 and NK3 receptors, respectively, had no effect. Contraction evoked by NKA was inhibited by the nonpeptide NK2 antagonist SR 48968 but not by the nonpeptide NK1 receptor antagonist CP-96,345, tetrodotoxin, or atropine. SR 48968 did not affect the response to carbachol.

CONCLUSIONS

Tachykinins contract the circular muscle of human esophageal body by activation of NK2 receptors without involvement of neural mechanisms. Response to SP is modulated by a phosphoramidon-sensitive enzymatic activity.

摘要

背景

速激肽在人食管体环行肌中的作用尚不清楚。本研究旨在确定对速激肽的反应以及介导该反应的受体类型。

方法

标本取自器官捐献者或因癌症接受食管切除术的患者，并测量对速激肽的等长张力。

结果

P物质（SP）、神经激肽A（NKA）和神经激肽B（NKB）引起浓度依赖性收缩，其效力顺序如下：NKA＞NKB＞SP。中性内肽酶抑制剂磷酰胺素仅增强对SP的反应。[β丙氨酸8]NKA（4-10），一种NK2受体的选择性激动剂，产生浓度依赖性收缩，而[Sar9，Met（O2）11]SP和[MePhe7]NKB，分别为NK1和NK3受体的选择性激动剂，则无作用。NKA引起的收缩被非肽类NK2拮抗剂SR 48968抑制，但不被非肽类NK1受体拮抗剂CP-96,345、河豚毒素或阿托品抑制。SR 48968不影响对卡巴胆碱的反应。