血管活性肠肽受体在人食管下括约肌中的表达及功能

Expression and function of vasoactive intestinal peptide receptors in human lower esophageal sphincter.

作者信息

Jia Tao, Zhao Ning

机构信息

Department of Thoracic Surgery, Handan Central Hospital, Handan, China.

The Eighth Department of General surgery, Handan Central Hospital, Handan, China.

出版信息

Ann Palliat Med. 2021 Mar;10(3):3067-3077. doi: 10.21037/apm-21-193.

DOI:10.21037/apm-21-193

PMID:33849096

Abstract

BACKGROUND

Vasoactive intestinal peptide (VIP) is an important neurotransmitter involved in the modulation of gastrointestinal function through the stimulation of VIP receptors. However, the expression of VPAC1R, VPAC2R and PAC1R in the human Lower esophageal sphincter (LES) has not been fully clarified. Therefore, the purpose of this study is to explore the expression of these receptors in the human Lower esophageal sphincter, the responses of the Lower esophageal sphincter to Vasoactive intestinal peptide, and the role of Vasoactive intestinal peptide receptors in the responses.

METHODS

Sling and clasp fiber samples of LES were acquired from patients undergoing subtotal esophagectomy, while circular muscle bundles from the esophagus and gastric fundus were used as control groups. Western blotting and RT-PCR technology were performed to determine the expression of the three VIP receptor subtypes. The isometric tension responses of the muscle sample strips to Ro25-1553 and PG99-465, and the effect of electrical field stimulation (EFS) on the sling and clasp fibers were studied.

RESULTS

We found that VPAC2R messenger RNA (mRNA) and protein were expressed in the sling and clasp fibers of human LES. However, no VPAC1R or PAC1R mRNA and protein expressions were found in the LES samples. The sling and clasp fibers of the LES produced significant concentration-dependent relaxation following exposure to Ro25-1553 and EFS could induce them to produce frequency-dependent relaxation. Furthermore, the relaxation responses of the LES were inhibited by PG99-465 and induced by EFS and Ro25-1553.

CONCLUSIONS

VPAC2R, but not VPAC1R or PAC1R, is expressed by the human LES. The relaxation responses of the LES generated by the VIP receptor agonist Ro25-1553 and EFS could be inhibited by the selective VPAC2 receptor antagonist PG99-465. VPAC2R may be important for the generation of relaxation and functional regulation of the LES.

摘要

背景

血管活性肠肽（VIP）是一种重要的神经递质，通过刺激VIP受体参与胃肠道功能的调节。然而，VPAC1R、VPAC2R和PAC1R在人下食管括约肌（LES）中的表达尚未完全阐明。因此，本研究的目的是探讨这些受体在人下食管括约肌中的表达、下食管括约肌对血管活性肠肽的反应以及血管活性肠肽受体在这些反应中的作用。

方法

从接受食管次全切除术的患者获取LES的吊带和扣状纤维样本，同时将食管和胃底的环形肌束用作对照组。采用蛋白质印迹法和逆转录-聚合酶链反应（RT-PCR）技术来测定三种VIP受体亚型的表达。研究了肌肉样本条对Ro25-1553和PG99-465的等长张力反应，以及电场刺激（EFS）对吊带和扣状纤维的影响。

结果

我们发现VPAC2R信使核糖核酸（mRNA）和蛋白质在人LES的吊带和扣状纤维中表达。然而，在LES样本中未发现VPAC1R或PAC1R的mRNA和蛋白质表达。LES的吊带和扣状纤维在暴露于Ro25-1553后产生显著的浓度依赖性舒张，并且EFS可诱导它们产生频率依赖性舒张。此外，LES的舒张反应受到PG99-465的抑制，并由EFS和Ro25-1553诱导。