Overview of P2 receptors: Possible functions in immune cells

P2 nucleotide receptors are subdivided into two families: P2X ionotropic ligand-gated ion channel receptors and P2Y metabotropic G-protein-coupled receptors. Seven subtypes of each family have been cloned and characterized. Immune cells are richly supplied by purinoceptors and there is a dominant presence of P1 (A(2A)), P2X(7), P2Y(1), and P2Y(2) receptors. Their mediating roles include: release of prostanoids and inflammatory cytokines; cell proliferation, growth, differentiation, fusion, and death; chemoattraction; cell adhesion and immuno-endothelial cell interactions; bone remodeling (osteoclasts); platelet aggregation; and wound healing, as well as regulation of immune responses. There is plasticity of P2 receptor expression in immune cells during development and after growing in culture. Examples include: the expression of P2Y(2) receptors in mature, but not developing, monocytes and the decline in P2Y(2) mRNA during monocyte to macrophage maturation. Inflammatory mediators have been shown to upregulate P2X(7) receptors and downregulate P2Y(2) receptors. The possible cellular sources of ATP acting on receptors on immune cells are considered, as well as some other questions about mechanisms involving P2 receptors. Therapeutic strategies for drug developments related to purinergic signaling in immune systems are considered. (C) 2001 Wiley-Liss, Inc.