NEURONAL SYNTHESIS, STORAGE AND RELEASE OF ATP

Adenosine 5'-triphosphate (ATP) is a ubiquitous substance in the centr al and peripheral nervous system. Nerve terminal ATP is generated from ADE: during glycolysis, citric acid cycle and predominantly by oxidat ive phosphorylation in the mitochondria. The adenine ring is synthesiz ed via de-novo purine biosynthesis, and also by purine salvage pathway s. The main regulator of ATP synthesis is ADP, the signal of the actua l energy state of the neuron. It inhibits (negative feedback) its own synthesis and also regulates mitochondrial oxidative phosphorylation. Storage of ATP has been shown in all types of synaptic vesicles and it can also be found in the cytoplasm in millimolar range. ATP cam be co -packaged with other neurotransmitters such as acetylcholine and norad renaline and may be stored in purinergic vesicles and, perhaps, in pur inergic nerve endings. Various treatments can alter vesicular composit ion, and hence, vesicular neurotransmitter/ATP ratio. There is now wid e acceptance that ATP is released stimulation-dependently from nerve e ndings of a number of isolated tissues and preparations upon depolariz ing stimuli. In addition to presynaptically derived ATP, ATP release f rom activated target cells in response to the action. of primary trans mitter on postsynaptic receptors also forms a significant contribution to neuronal outflow in several tissues. As for the possible role of i ntraterminal ATP pools in the release process, recent observations sup port the view that ATP is released as a genuine cotransmitter or as a principal purinergic neurotransmitter in an exocytotic way, but also i ndicate the involvement of other neuronal pools of ATP in the release, such as carrier-mediated release from the cytoplasm. (C) 1996 Academi c Press Ltd