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

M Liu1, A L Kirchgessner

  • 1Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York, 11203, USA.

Insights

Metabotropic glutamate receptor 5 (mGluR5) is found in guinea pig ileum neurons, particularly secretomotor neurons. Its internalization regulates enteric nervous system reflexes, suggesting a key role for mGluR5 in gut function.

Area of Science:

  • Neuroscience
  • Gastroenterology
  • Pharmacology

Background:

  • Metabotropic glutamate receptor 5 (mGluR5) is implicated in neuronal function.
  • The role of mGluR5 in the enteric nervous system (ENS) is not fully understood.

Purpose of the Study:

  • To investigate the presence and function of mGluR5 in the guinea pig ileum.
  • To explore the mechanisms regulating mGluR5 activity in enteric neurons.

Main Methods:

  • Immunocytochemistry and confocal microscopy to localize mGluR5.
  • Pharmacological inhibition of mGluR5 internalization and activity.
  • Measurement of cAMP-responsive element-binding protein phosphorylation and neuronal responses.

Main Results:

  • mGluR5 is localized to the plasma membrane of a subset of guinea pig ileum submucosal neurons, predominantly noncholinergic secretomotor neurons.
  • Agonist- and reflex-evoked mGluR5 internalization was observed and inhibited by a group I antagonist.
  • Group I mGluR antagonists reduced distension-induced signaling and attenuated excitatory responses in submucosal neurons.

Conclusions:

  • mGluR5 is present and functional in the guinea pig ileum's enteric nervous system.
  • Internalization is a key mechanism for regulating mGluR5 activity in enteric reflexes.
  • mGluR5 antagonists show potential for modulating gut functions.

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