Agonist- and Reflex-Evoked Internalization of Metabotropic Glutamate Receptor 5 in Enteric Neurons

• Published in: The Journal of neuroscience Vol. 20; no. 9; pp. 3200 - 3205
• Main Authors: Liu, Min-tsai, Kirchgessner, Annette L
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01.05.2000; Society for Neuroscience
• Subjects: Animals; Enteric Nervous System - metabolism; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Glutamic Acid - pharmacology; Guinea Pigs; Ileum - metabolism; Male; Methoxyhydroxyphenylglycol - analogs & derivatives; Methoxyhydroxyphenylglycol - pharmacology; Neurons - metabolism; Receptor, Metabotropic Glutamate 5; Receptors, Metabotropic Glutamate - agonists; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - metabolism; Submucous Plexus - metabolism
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.20-09-03200.2000

We demonstrate that metabotropic glutamate receptor 5 (mGluR5) is present in the guinea pig ileum. A punctate ring-like distribution of immunoreactivity is found on the soma of a subset of neurons, consistent with an association of mGluR5 with the plasma membrane. mGluR5-containing cells in the submucosal plexus are predominantly noncholinergic and contain vasoactive intestinal 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 antagonists reduce the distension-induced phosphorylation of cAMP-responsive element-binding protein in enteric neurons and attenuate both glutamate- and group I agonist-induced depolarizing responses and slow synaptic events in submucosal neurons. These findings support the idea that mGluRs play a role in enteric reflexes and suggest that internalization might be a major mechanism for regulation of mGluR activity.