Distribution of P2X₃ receptor immunoreactivity in myenteric ganglia of the mouse esophagus

Intraganglionic laminar endings (IGLEs) represent the major vagal afferent terminals throughout the gut. Electrophysiological experiments revealed a modulatory role of ATP in the IGLE-mechanotransduction process and the P2X₂-receptor has been described in IGLEs of mouse, rat and guinea pig. Another purinoceptor, the P2X₃-receptor, was found in IGLEs of the rat esophagus. These findings prompted us to investigate occurrence and distribution of the P2X₃-receptor in the mouse esophagus. Using multichannel immunofluorescence and confocal microscopy, P2X₃-immunoreactivity (-iry) was found colocalized with the vesicular glutamate transporter 2 (VGLUT2), a specific marker for IGLEs, on average in three-fourths of esophageal IGLEs. The distribution of P2X₃ immunoreactive (-ir) IGLEs was similar to that of P2X₂-iry and showed increasing numbers towards the abdominal esophagus. P2X₃/P2X₂-colocalization within IGLEs suggested the occurrence of heteromeric P2X₂/₃ receptors. In contrast to the rat, where only a few P2X₃-ir perikarya were described, P2X₃ stained perikarya in ~80% of myenteric ganglia in the mouse. Detailed analysis revealed P2X₃-iry in subpopulations of nitrergic (nNOS) and cholinergic (ChAT) myenteric neurons and ganglionic neuropil of the mouse esophagus. We conclude that ATP might act as a neuromodulator in IGLEs via a (P2X₂)-P2X₃ receptor-mediated pathway especially in the abdominal portion of the mouse esophagus.