Pathophysiological Role of Extracellular Purinergic Mediators in the Control of Intestinal Inflammation

Table 1

Recent reports indicating the critical roles of eATP in the adverse conditions of intestines (inflammatory bowel diseases and irritable bowel syndrome).

Enteric diseases	Receptors	Functions	Reference
Inflammatory bowel disease	P2R/A2BR	Enhance co-transmigration of neutrophils and platelets across intestinal epithelial cells in IBD patients. Platelets release large amount of ATP in the lumen metabolite to adenosine via CD73 and ecto-NTPDases expressed in epithelial cells. Adenosine-A2BR pathway induces electrogenic Cl-secretion with water movement to lumen.	[37]
	P2XR	T cell receptor stimulation induces ATP synthesis and release from activated T cells through pannexin-1 hemichannels. Released ATP activates T cells and produce IL-2 and proliferation in autocrine manner. Blockage of P2X receptors (oxidative ATP) impairs the development of colitis in mice.	[38]
	P2R	ATP released from commensal bacteria acts on CD70+ CD11c+ cells reside in the intestinal lamuna propria and induces Th17 cells in mice; degradation of ATP (by apyrase treatments) ameliorates colitis in mice.	[9]
	P2Y2	Increase of P2Y2 expression in epithelial cells is observed during colitis. P2Y2 stimulation induces release of prostaglandin E2 release from the cells and promotion of intestinal microtubule stabilization and mucosal reepithelization. Those pathways take part in the wound healing during colonic inflammation. Treatment with P2Y2 agonist improves recovery from colitis in mice.	[39]
	P2X7	ATP induces activation of mast cells and enhances inflammatory responses, upregulation of P2X7 in mast cells of Crohn's disease patients, anti-P2X7 antibody treatment inhibits colitis in mice.	[40]
	P2X7	Induction of enteric neuronal cell death and alteration of intestinal motility.	[41]
	P2R	ATP induces IL-6 and CXCL1 productions from epithelial cells; ATP influences the response of epithelial cells to various TLR ligands and induces inflammatory T cells by affecting DC maturations.	[42]
	P2X7	Prophylactic systemic P2X7 blockade (A740003 and brilliant blue G) reduces inflammatory cytokines in rats.	[43]
	P2X7	Upregulation of P2X7 in epithelium, macrophage, and dendritic cells of Crohn's disease patients, P2X7-deficient mice did not develop colitis.	[44]
Irritable bowel syndrome	P2X7	Induction of IL-1 and the development of postinflammatory visceral hypersensitivity in the Trichinella  spiralis-infected mouse	[34]