Purinergic P2X(7) receptor: A pivotal role in inflammation and immunomodulation

Many, potentially all, inflammatory and immune cells express purinergic rec eptors of the P1 and P2 type. In recent years, availability of molecular pr obes and, in some cases, specific antibodies has initiated an investigation of their possible involvement in the inflammatory response. A very recent acquisition is that, besides expressing purinergic receptors, immune cells also secrete ATP, that, once in the extracellular milieu, undergoes hydroly sis by various hydrolases or kinases. Besides active secretion, ATP can als o leak into the pericellular space as a consequence of cell damage. Althoug h adenosine appears to have a preeminent anti-inflammatory activity, ATP by means of the P2X(7) receptor seems to act as a proinflammatory mediator, a cytotoxic factor, or both. The combined activity of adenosine and ATP prov ides means for a fine modulation of the inflammatory response, depending on the amount of extracellular ATP, the rate of hydrolysis and the level of e xpression of P2 and P1 receptors. The P2X(7) receptor appears to be involve d in several processes relevant to inflammation (interleukin-1 beta release , cytotoxicity, formation of macrophage polykarions), thus, it may be an ap pealing target for pharmacologic intervention. Drug Dev. Res. 45:207-213, 1 998. (C) 1998 Wiley-Liss, Inc.