Purinergic neurotransmission and nucleotide receptors

Adenosine 5′-triphosphate (ATP) is a neurotransmitter of postganglionic sympathetic nerves and nonadrenergic, noncholinergic nerves of the enteric nervous system. ATP can also modulate autonomic reflexes through actions at sensory afferent nerves. Mechanisms exist within nerves for the vesicular storage and exocytotic release of ATP. Once released, the availability and duration of ATP is regulated by cell surface ectonucleotidases that hydrolyze ATP, producing metabolites including ADP and adenosine in the process. The effects of ATP are mediated via activation of cell surface purinergic receptors, namely, P2X and P2Y receptors. P2X receptors are ligand-gated nonselective cation channels activated by ATP and causing membrane depolarization and elevation in intracellular Ca2+. P2Y receptors are G protein-coupled receptors activated by ATP and ADP. Signal transduction mechanisms of P2Y receptors including intracellular Ca2+ signaling and inhibition of adenylate cyclase activity. Postjunctional P2X and P2Y receptors effect neurotransmission by ATP, whereas prejunctional receptors are capable of modulating neurotransmitter release