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The Journal of Neuroscience, May 1, 2000, 20(9):3200-3205

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

Min-tsai Liu and Annette L. Kirchgessner

Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York, 11203

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.

Key words: glutamate; electrophysiology; DHPG; CHPG; AIDA; S-4CPG; MPEP; pCREB

Copyright © 2000 Society for Neuroscience  0270-6474/00/2093200-06$05.00/0


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