Schematic representation of the conditions which can lead to P2 receptor (P2R) activation in the nervous (a) and cardiovascular (b) systems. Tissue trauma, stress, mechanical injury, infection, and autoimmune disorders, among others, can lead to increased extracellular levels of ATP and/or proinflammatory cytokines. Extracellular ATP diffuses to activate neighboring cells by paracrine and autocrine pathways. In this context signaling through the P2 receptor may allow cells to sense and respond to events occurring in the extracellular environment, modulate the transcription of genes involved in cellular inflammatory processes, and thus regulate cytokine responses. The P2 receptor may function as an amplification device to spread the ATP wave as its activation triggers further ATP (and proinflammatory mediator) release, culminating in pathology. These characteristics, coupled with the broad distribution of P2 receptors encourage the therapeutic exploitation of this target. AD Alzheimer's disease.