Differential Regulation of P2X7 Receptor Activation by Extracellular Nicotinamide Adenine Dinucleotide and Ecto-ADP-Ribosyltransferases in Murine Macrophages and T Cells

摘要: Extracellular NAD induces the ATP-independent activation of ionotropic P2X 7 purinergic receptor (P2X R) in murine T lymphocytes via a novel covalent pathway involving ADP-ribosylation arginine residues on R ectodomain. This modification is catalyzed by ART2.2, GPI-anchored ADP-ribosyltransferase (ART) that constitutively expressed cells. We previously reported ART2.1, related ecto-ART, up-regulated inflammatory macrophages express R. Thus, we tested hypothesis extracellular acts ART2.1 to regulate function macrophages. Coexpression cloned with or ART2.2 HEK293 cells verified an equivalent substrate for either ART2.2. However, contrast cells, stimulation alone did not activate Rather, potentiated ATP-dependent as indicated left shift ATP dose-response relationship. regulates both and but distinct mechanisms. Although sufficient gate channel opening this does decreases threshold gating response binding. These findings indicate can act synergistically signaling also suggest cellular context which occurs differs between myeloid lymphoid leukocytes.