Emodin (1,3,8-trihydroxy-6-methylanthraquinone), an anthraquinone derivative from Rheum officinale Baill, exhibits anti-inflammatory and immunosuppressive activities, however, the underlying mechanisms are not fully understood. This study examined the effects of emodin on ATP-evoked responses in rat peritoneal macrophages and in human embryonic kidney 293 cells (HEK293) heterologously expressing the cloned rat P2X7 receptor. Emodin reduced macrophage death induced by millimolar ATP in a concentration-dependent manner with the half of maximal inhibition values (IC50) of 0.2 microM. It also strongly inhibited ATP-induced dye uptake or pore formation, a hallmark property associated with P2X7 receptor activation, and 2',3'-O-(benzoyl-4-benzoyl)-ATP (BzATP) induced increases in intracellular Ca2+ concentrations in macrophages with an IC50 of 0.5 microM. Furthermore, emodin significantly suppressed BzATP-evoked currents in P2X7 receptor expressing HEK293 cells with an IC50 of 3.4 microM. Taken together, these results provide compelling evidence for a novel action of emodin as a P2X7 receptor antagonist, which may underlie its anti-inflammatory and immunosuppressive activities.
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