Neurotransmission by ATP: new insights, novel mechanisms

Purines have long been known for their roles in extracellular signaling. One of the most interesting functions to come to light recently has been the involvement, particularly of adenosine 5'-triphosphate (ATP), as a neurotransmitter in the central and the sympathetic nervous system. ATP is stored in and released from synaptic nerve terminals, like other neurotransmitters, and is known to act post-synaptically via specific rapidly-conducting, ligand-gated ion channels, the P2x receptors. Another interesting feature is the discovery that ATP is widely found to be a "co-transmitter" at the same synapses in combination with other neurotransmitters such as noradrenaline, acetylcholine, and GABA, altering our picture of the biophysics and biochemistry of neurotransmission at these synapses. We describe here these and other aspects of neurotransmission by ATP being investigated vigorously today, including recent findings on P2x receptors and those on the synaptic inactivation of ATP by ecto-ATPase. We conclude by pointing out possible pharmacological and clinical implications of neurotransmission by ATP.