Presynaptic P2X2/3 receptors mediate extracellular ATP-triggered glutamate release in the nucleus of the solitary tract

Abstract

Activation of ATP-gated receptor channels (P2X receptors) facilitates glutamate release and excites postsynaptic neurons in the nucleus of the solitary tract (NTS) (Shigetomi & Kato, 2004). The subtype of P2X receptor underlying this transduction of extracellular ATP signal to excitatory transmission enhancement remains unidentified. To address this issue, we analyzed the effects of agonists and antagonists of P2X on this release facilitation in brain slices. The following lines of evidence strongly argue for a possible involvement of P2X2/3 heteromeric receptors: (1)a P2X3-selective antagonist, A-317491 (3 μM), suppressed this facilitation, (2) space- and time-delimited ATP application with laser photoactivation of caged ATP induced rapid onset and persistent facilitation, (3) the release facilitation with αβmATP, in a manner sensitive to TNP-ATP (10 μM), was observed in mice lacking P2X4 subunits. As P2X2 subunits has been selectively localized on the primary afferent termini in the NTS, this conclusion implies that extracellular ATP-triggered glutamate release in the NTS could mimic vagal afferent signal in response to changes in the intracranial environment including astrocyte network excitation that could result in ATP release onto perisynaptic space. [J Physiol Sci. 2008;58 Suppl:S49]