The P2Z/P2X7 receptor of microglial cells: A novel immunomodulatory receptor

This chapter investigates the role of the P2X7 receptor, formerly also known as P2Z, in microglia activation. The chapter presents the first evidence in support of the expression by microglial cells of an ATP-gated plasma membrane pore closely resembling the macrophage P2Z receptor. This was inferred on the basis of the ability of ATP to cause (1) fast plasma membrane depolarization, (2) uptake of ethidium bromide or lucifer yellow, and (3) release of cytoplasmic markers (e.g., lactate dehydrogenase), responses generally accepted as functional evidence for the expression of P2Z. This strong but indirect evidence was then confirmed by immunoblot analysis with an antiserum raised against the COOH tail of the P2X7 receptor that is in the meantime cloned from a rat brain library. A detailed investigation in the CNS gave no evidence for the presence of P2X7 in central neurons, thus suggesting that this receptor might have been originally cloned from microglia. The finding of a P2Z/P2X7 type receptor in microglia is consistent with the known peculiar expression of this molecule by immune cells and by mononuclear phagocytes.