Extracellular ATP and the related purine and pyrimidine nucleotides exert their functions via signaling through membrane-bound purinergic P2 receptors. These receptors are widely expressed throughout the body on various immune and nonimmune cells. The P2 receptors are subdivided into two families: the G protein-coupled P2Y receptors and the ligand-gated P2X ion channels. The International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification recognizes eight distinct P2Y receptor subtypes: P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14 and seven P2X subunits that may form six homomeric (P2X1–P2X5 and P2X7), and at least six heteromeric P2X1/2, P2X1/4, P2X1/5, P2X2/3, P2X2/6, and P2X4/6, receptors. Either constitutively present or induced under pathological conditions, P2 receptors are differentially expressed on a large scale of cells including immune cells. Although P2 receptors are clearly implicated in diverse inflammatory reactions, the mechanisms involved are complex and not fully elucidated. Their expression profiles and biological activities are diverse as evidenced by results in the literature regarding eosinophils, neutrophils, mast cells, monocytes/macrophages, lymphocytes, and others. Identifying the precise receptors and pathways involved is a first step in the challenge which could lead to the discovery of a new therapeutic class of drugs that suppress inflammation.

References

1.Jacob F, et al. Purinergic Signal. 2013;9(3):285–306.