Enteric nervous system and inflammatory bowel diseases: Correlated impacts and therapeutic approaches through the P2X7 receptor

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.