High level of extracellular ATP from the damaged cells enforces microglia to undergo chemotaxis to the site of injury in order to remove cell debris from these sites.12 Microglial activation13 results in upregulation of P2X4 and P2X7 14,15 and downregulation of P2Y12 receptor expression.16 This balance between the expression of P2X4, P2X7, and P2Y12 receptors dictate the destiny of microglia.17 A relative expression levels of P2X4 and P2X7 receptors are positive indicator of microglial activation, while P2Y12 receptor is a negative predictor.18 Additionally, upon release of the large amount of ATP (hundreds of μmol), P2Y1 and P2X7 receptors facilitate movement of ramified microglia to the damage site, while P2Y6 receptor, a normally expressed receptor on the activated microglia, intervenes the process of phagocytosis.3,19 Furthermore, extracellular ATP can be converted to adenosine via ectonucleotidases CD39 and CD73 that are present in microglia20 and in turn activates ARs as well.21,22
