Axon terminal P2-purinoceptors in feedback control of sympathetic transmitter release

Extracellular ATP acts on P2-purinoceptors of peripheral effector cells, and this is the basis for its function as a (co-)transmitter in peripheral efferent neurons. ATP also acts on P2-receptors of neuronal cell bodies or dendrites, and this is the basis for its function as a fast excitatory transmitter at neuroneural synapses. A third site of action is axon terminals. In the vas deferens of the mouse, noradrenaline and ATP are postganglionic sympathetic co-transmitters, and exogenous ATP acts on P2-purinoceptors of the sympathetic terminals to inhibit release of noradrenaline. Here we show that two P2 antagonists, suramin and Reactive Blue 2, increase the release of noradrenaline in mouse vas deferens. The increase is only obtained when there has been preceding nerve activity and is largely independent of the postjunctional response. These findings indicate a physiological function for axon terminal P2-purinoceptors: they mediate a novel prejunctional negative feedback in which released ATP inhibits subsequent transmitter release.