NUCLEOTIDES AS EXTRACELLULAR SIGNALING MOLECULES

There is now wide acceptance that ATP and other nucleotides are ubiquitous extracellular chemical messengers. ATP and diadenosine polyphosphates can be released from synaptosomes. They act on a large and diverse family of P2 purinoceptors, four of which have been cloned. This receptor family can be divided into two distinct classes: ligand-gated ion channels for P2X receptors and G protein-coupled receptors for P2Y, P2U, P2T and P2D receptors. The P2Y, P2U and P2D receptors have a fairly wide tissue distribution, while the P2X receptor is mainly found in neurons and muscles and the P2T and P2Z receptors confined to platelets and immune cells, respectively. Inositol phosphate and calcium signalling appear to be the predominant mechanisms for transducing the G-protein linked P2 receptor signals. Multiple P2 receptors are expressed by neurons and glia in the CNS and also in neuroendocrine cells. ATP and other nucleotides may therefore have important roles not only as a neurotransmitter but also as a neuroendocrine regulatory messenger.