Extracellular ATP operates as a strong enhancer of membrane blebbing and shedding upon activation of its receptor P2X7, a low-affinity ion channel widely expressed in the nervous and immune system. For this reason, exATP is widely recognized as an important candidate for explaining the above observation. In the nervous system exATP can be found after secretion by microglia cells (27, 37, 38), after release from astrocytes through the activated P2X7 and/or pannexin-1 (38, 39), or after cell death (40). Among the known receptors of purines, only P2X7 has been recognized to sustain the generation of MVs (13). Compared to the other members of the P2X family, such as P2X1 and P2X3 (EC50 = 10 µM), P2X7 has the lowest affinity for ATP (EC50 = 500 µM) (41). Therefore, high amounts of exATP are needed to activate P2X7 and trigger the production of MVs. Indeed ATP, abundantly released from degenerating cells during inflammation, is assumed to be rapidly transformed into ADP, AMP and adenosine by efficient cell surface-resident enzymes, known as ecto-ATPases (such as CD39 and CD73). These changes may reduce the ability of exATP to activate the P2X7 receptor in chronic inflammation (42).