Expression of P2X6 receptors in the enteric nervous system of the rat gastrointestinal tract

Expression of P2X4 and P2X6 receptor subunits in the gastrointestinal tract of the rat was studied with double-labeling fluorescence immunohistochemistry. The results showed that P2X6 receptors were expressed widely in the submucosal and myenteric plexuses. In the myenteric plexus, P2X6 receptors were expressed mainly in large size neurons which resembled Dogiel type II neurons. These P2X6 receptor-immunoreactive (ir) neurons also expressed calbindin 28K, calretinin and neuronal nuclei (NeuN), proteins that are markers of intrinsic sensory neurons. In the submucosal plexus, all the calbindin 28K, calretinin and NeuN-ir cells were immunoreactive for P2X6 receptors. P2X6 receptors do not form homomultimers, but rather heteromultimers with either P2X2 or P2X4 receptors. P2X4 receptors were not expressed in neurons, but were expressed in macrophages of the rat gastrointestinal tract. These data indicate that P2X6 receptors are mainly expressed on intrinsic sensory neurons and that ATP, via P2X6 receptors probably in heteromeric combination with P2X2 receptors, may be involved in regulating the physiological functions of these neurons.