P2X(7) receptor at the heart of disease.

Purinergic signaling is a crucial component of disease whose pathophysiological basis is now well established. This review focuses on P2X(7), a unique bifunctional purinoreceptor that either opens a non selective cation channel or forms a large, cytolytic pore depending on agonist application and leading to membrane blebbing and to cell death either by necrosis or apoptosis.Activation of P2X(7) receptor has been shown to stimulate the release of multiple proinflammatory cytokines by activated macrophages, with the IL-1b to be the most extensively studied among them. These findings were verified by the use of knockout P2X(7) ((-/-)) mice.Update information coming from all fields of research implicate this receptor at the very heart of diseases such as rheumatoid arthritis, multiple sclerosis, depression, Alzheimer disease, and to kidney damage, in renal fibrosis and experimental nephritis.Clinical studies are currently underway with the newly developed selective antagonists for P2X(7) receptor, the results of which are eagerly anticipated. These studies together with data from in-vivo experiments with the P2X(7) knockout mice and in-vitro experiments will shed light in this exciting area.