The P2Y4R is present in all cells of the brain, including neurons,268 astrocytes,269 and microglia.270 However, the functional role of the receptor is still ambiguous. It is believed that P2Y4 R might complement the P2Y2R since both receptors are present in glial end feet in vicinity of the blood vessel walls.271 Human P2Y4R is stimulated by UTP (EC50 = 73 nM), but not by ATP.272 However, both nucleotides activate the rat and mouse P2Y4 receptors. In microglia, P2Y4 receptors are involved in ATP triggered pinocytosis that results in the uptake of soluble Aβ1-42, and either P2Y4 knockdown or ATP deficiency has shown to decrease this process.273 Hence, in addition to the P2Y12 receptor-mediated “find me” signal16 and the P2Y6 receptor-mediated “eat me” signal,233 P2Y4 receptors facilitate “drink me” signal that enables uptake of soluble Aβ by microglia.273 Therefore, activation of P2Y4 receptor in AD may have a neuroprotective effect possibly through uptake of Aβ1-42. 273,274
