Randomized Controlled Trial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2017; 23(34): 6339-6349
Published online Sep 14, 2017. doi: 10.3748/wjg.v23.i34.6339
P2Y1R is involved in visceral hypersensitivity in rats with experimental irritable bowel syndrome
Jie Wu, Yan Cheng, Rong Zhang, Dong Liu, Yu-Mei Luo, Kun-Lun Chen, Song Ren, Jun Zhang
Jie Wu, Yan Cheng, Dong Liu, Jun Zhang, Department of Gastroenterology, The Second Affiliated Hospital of School of Medicine, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Rong Zhang, Department of Gastroenterology, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
Yu-Mei Luo, Department of Gastroenterology, The First Affiliated Hospital of School of Medicine, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Kun-Lun Chen, Song Ren, Fourth Cadre Ward, The Second Affiliated Hospital of School of Medicine, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Author contributions: Wu J and Zhang J designed the research; Wu J, Cheng Y, Luo YM and Chen KL performed the research; Zhang R and Ren S contributed new reagents or analytic tools; Liu D analyzed the data; Wu J and Zhang J wrote the paper.
Supported by MIMS (Shanghai) Ltd. of China, No. IDF-2013-07.
Institutional review board statement: This study was approved by the Institutional Review Board of Medicine College of Xi’an Jiaotong University.
Institutional animal care and use committee statement: The study was approved by Ethical Committee of Xi’an Jiaotong University.
Conflict-of-interest statement: None declared.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Jun Zhang, Department of Gastroenterology, The Second Affiliated Hospital of School of Medicine, Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an 710004, Shaanxi Province, China. junzh3z@163.com
Telephone: +86-13572955788 Fax: +86-29-87679272
Received: March 28, 2017
Peer-review started: April 1, 2017
First decision: April 26, 2017
Revised: May 15, 2017
Accepted: June 19, 2017
Article in press: June 19, 2017
Published online: September 14, 2017
Processing time: 169 Days and 18.3 Hours
Abstract
AIM

To evaluate the role of P2Y1R in visceral hypersensitivity in rats with experimental irritable bowel syndrome.

METHODS

A rat model of irritable bowel syndrome was generated by intra-colonic administration of acetic acid (AA) and assessed by histology and myeloperoxidase (MPO) activity assay. Then P2Y1R expression in the colonic tissue was detected by Western blot. In order to explore the regulatory role of P2Y1R in visceral hypersensitivity, an agonist (MRS2365) and an antagonist (MRS2179) of P2Y1R were intra-colonically administered and effects were tested through a colorectal distension test. The abdominal withdrawal reflex and abdominal electromyography were tested during the course.

RESULTS

Model assessment tests showed an obvious inflammatory reaction that appeared on the 2nd d after the AA injection, and the inflammatory reaction gradually recovered and almost disappeared on the 7th d. The model finished on day 8 and showed a clear feature of IBS that had no organic lesion. The average expression of P2Y1R was significantly higher in the AA group than in the naïve group (0.319 ± 0.02 vs 0.094 ± 0.016, P < 0.001). MRS2365 could effectively raise the colonic hypersensitivity status at intervention doses of 10 (AUC value from 0.30 ± 0.089 to 1.973 ± 0.127 mv·s, P < 0.01) and 100 μmol/L (AUC value from 0.290 ± 0.079 to 1.983 ± 0.195 mv·s, P < 0.01); MRS2179 could effectively reduce the hypersensitivity status at intervention dose of 100 μmol/L (from a mean baseline AUC value of 1.587 ± 0.099 mv·s to 0.140 ± 0.089 mv·s, P < 0.0001). Differences between the MRS2179 group (1.88 ± 1.45) and either the MRS2365 group (3.96 ± 0.19) or the combined treatment (MRS2179 and MRS2365) group (3.28 ± 0.11) were significant (P < 0.01).

CONCLUSION

P2Y1R plays a regulatory role in visceral hypersensitivity in rats with experimental IBS. Specific antagonists of P2Y1R may have potential therapeutic value in treating abdominal pain in IBS.

Keywords: Irritable bowel syndrome; P2Y1 receptor; Regulation; Therapy; Visceral hypersensitivity

Core tip: P2Y1R is believed to be part of a high-sensitivity response to mechanical stimulation but whether it is involved in visceral hypersensitivity of irritable bowel syndrome is discussing. We detected its expression in the colon of a rat model of irritable bowel syndrome, and explored its regulatory role in visceral hypersensitivity with a specific agonist and an antagonist. The abdominal withdrawal reflex and electromyography tests showed effective changes after intervention. It was interesting to note that in case of combined treatment of the two drugs, the antagonist showed higher effects, which indicated that other P2 receptors might be involved in the hypersensitivity of irritable bowel syndrome.