[Pharmacological effects and metabolism of extracellular ATP]

Cells are equipped with complex mechanisms for synthesis of ATP and try to keep the intracellular level of this compound, which is indispensable for maintenance of normal function and integrity, as constant as possible. Thus, it is generally believed that ATP rarely cross the plasma membrane of viable cells. However, since the first report of Holton in 1959, the release of nucleotides from cells has become an established fact, and the physiological role and metabolism of the released ATP has become an important topic; potent actions of extracellular purine nucleotides and nucleosides have been recognized for many years. In 1972, Burnstock demonstrated that ATP has a transmitter role in certain types of nerves and proposed a concept of purinergic nerve. The receptor for purine nucleotides, designated as P2, as opposed to P1, by Burnstock in 1978 was further subclassified in 1985 into P2X and P2Y by himself, and we now have a train of P2 receptors, such as P2S, P2T, P2Z and so forth. In this review, I summarized the characteristics of these purinoceptors. Pharmacological effects and metabolism of extracellular nucleotides were discussed and a brief mention was made of ecto-nucleotidases.