P2-Purinoceptors: Advances and therapeutic opportunities.

The recent cloning of a number of distinct receptors belonging to the P2-purinoceptor superfamily has provided conclusive evidence for a pivotal role for ATP and other nucleotides as effector molecules involved in cell-to-cell communication and the modulation of many basic aspects of tissue function. ATP itself is being clinically evaluated as a cytotoxic agent for the treatment of cancer and as an adjunct to inhalation anaesthetic use. The pyrimidine nucleotide, UTP, is in clinical trials for the treatment of cystic fibrosis. The stable ATP bioisostere, ARL 67085, is being developed as a novel antithrombotic agent, blocking with a superior safety profile and increased efficacy as compared to other agents. The diversity of P2 receptors, with eleven having been defined using both pharmacological and molecular cloning criteria, indicates considerable additional potential and subtlety in regard to the effects of ATP on tissue function and pathophysiology.