Agonist- and reflex-evoked internalization of metabotropic glutamate receptor 5 in enteric neurons

We demonstrate that metabotropic glutamate receptor 5 (mGluR5) is present i n the guinea pig ileum. A punctate ring-like distribution of immunoreactivi ty is found on the soma of a subset of neurons, consistent with an associat ion of mGluR5 with the plasma membrane. mGluR5-containing cells in the subm ucosal plexus are predominantly noncholinergic and contain vasoactive intes tinal peptide, a marker of secretomotor neurons. Using immunocytochemistry in conjunction with confocal microscopy, we show that the mGluR5 undergoes agonist-and reflex-evoked internalization that is inhibited by the group I antagonist 1-aminoindan-1,5-dicarboxylic acid. In addition, group I mGluR a ntagonists reduce the distension-induced phosphorylation of cAMP-responsive element-binding protein in enteric neurons and attenuate both glutamate- a nd group I agonist-induced depolarizing responses and slow synaptic events in submucosal neurons. These findings support the idea that mGluRs play a r ole in enteric reflexes and suggest that internalization might be a major m echanism for regulation of mGluR activity.