Purinergic inhibition of neurotransmitter release in the central nervous system

Neurotransmitter release and the role of adenosine in its regulation has been investigated for more than twenty years, and it is now widely accepted that adenosine tonically inhibits the release of excitatory neurotransmitters. This effect of adenosine is operated by an A1 adenosine receptor. Since activation of this receptor could inhibit Ca2+ conductance, increase K+ conductance, inhibit adenylate cyclase or phospholipase C, it is not clear if there is only one mechanism or several mechanisms operated by adenosine to inhibit neurotransmitter release, and in that case, what is the relative importance of each mechanism. The mechanism by which adenosine inhibits evoked synchronous transmitter release might be different from that used by the nucleoside to inhibit spontaneous asynchronous release. In some systems adenosine triphosphate per se acts like adenosine and inhibits neurotransmitter release. However, in most cases the inhibitory effect of this adenine nucleotide depends upon its hydrolysis into adenosine by a cascade of ectoenzymes, the last step being mediated by ecto-5'-nucleotidase.