Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2021; 27(46): 7909-7924
Published online Dec 14, 2021. doi: 10.3748/wjg.v27.i46.7909
Enteric nervous system and inflammatory bowel diseases: Correlated impacts and therapeutic approaches through the P2X7 receptor
Henrique Inhauser Riceti Magalhães, Patricia Castelucci
Henrique Inhauser Riceti Magalhães, Department of Surgery, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo 08000-000, Brazil
Patricia Castelucci, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 08000-000, Brazil
Author contributions: Magalhães HIR was responsible for the literature review and analysis and wrote the review; Castelucci P performed the critical interpretation and revised the manuscript for intellectual content.
Supported by the São Paulo Research (FAPESP, Brazil), No. 2014/25927-2 and No. 2018/07862-1; and the National Council for Scientific and Technological Development (CNPq, Brazil).
Conflict-of-interest statement: The authors declare no conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Patricia Castelucci, MHSc, PhD, Associate Professor, Associate Research Scientist, Lecturer, Department of Anatomy, University of São Paulo, Av. Dr Lineu Prestes, 2415, São Paulo 08000-000, Brazil. pcastel@usp.br
Received: July 10, 2021
Peer-review started: July 10, 2021
First decision: August 19, 2021
Revised: August 19, 2021
Accepted: November 25, 2021
Article in press: November 25, 2021
Published online: December 14, 2021
Processing time: 152 Days and 18.2 Hours
Abstract

The enteric nervous system (ENS) consists of thousands of small ganglia arranged in the submucosal and myenteric plexuses, which can be negatively affected by Crohn’s disease and ulcerative colitis - inflammatory bowel diseases (IBDs). IBDs are complex and multifactorial disorders characterized by chronic and recurrent inflammation of the intestine, and the symptoms of IBDs may include abdominal pain, diarrhea, rectal bleeding, and weight loss. The P2X7 receptor has become a promising therapeutic target for IBDs, especially owing to its wide expression and, in the case of other purinergic receptors, in both human and model animal enteric cells. However, little is known about the actual involvement between the activation of the P2X7 receptor and the cascade of subsequent events and how all these activities associated with chemical signals interfere with the functionality of the affected or treated intestine. In this review, an integrated view is provided, correlating the structural organization of the ENS and the effects of IBDs, focusing on cellular constituents and how therapeutic approaches through the P2X7 receptor can assist in both protection from damage and tissue preservation.

Keywords: Chemical coding; Enteric nervous system; Gastroenterology; Inflammatory bowel diseases; P2X7 receptor; Purinergic signaling

Core Tip: This review summarizes the impacts caused by inflammatory bowel diseases on enteric nervous system cells and brings together the findings of the most recent literature on therapeutic approaches through the P2X7 receptor. Despite the great advancement of knowledge in the field, data on the mechanisms and effects of neuronal loss during colitis are still scarce. Furthermore, clinical trials that would make the use of P2X7 receptor antagonists in human patients feasible are lacking. In the laboratory, the results of animal models reinforce that the P2X7 receptor may be an important future target for the treatment of intestinal disorders.