Agonist- and reflex-evoked internalization of metabotropic glutamate receptor 5 in enteric neurons.
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.
Liu
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Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York, 11203, USA.
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D000818:Animals; D017615:Enteric Nervous System / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013368:Submucous Plexus / Q000378:metabolism*
D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol