Differential regulation of metabotropic glutamate receptor 5-mediated phosphoinositide hydrolysis and extracellular signal-regulated kinase responses by protein kinase C in cultured astrocytes

J Neurochem. 2002 Oct;83(1):110-8. doi: 10.1046/j.1471-4159.2002.01113.x.


The metabotropic glutamate receptor 5 (mGluR5) exhibits a rapid loss of receptor responsiveness to prolonged or repeated agonist exposure. This receptor desensitization has been seen in a variety of native and recombinant systems, and is thought to result from receptor-mediated, protein kinase C (PKC)-dependent phosphorylation of the receptor, uncoupling it from the G protein in a negative feedback regulation. We have investigated the rapid PKC-mediated desensitization of mGluR5 in cortical cultured astrocytes by measuring downstream signals from activation of mGluR5. These include activation of phosphoinositide (PI) hydrolysis, intracellular calcium transients, and extracellular signal-regulated kinase 2 (ERK2) phosphorylation. We present evidence that PKC plays an important role in rapid desensitization of PI hydrolysis and calcium signaling, but not in ERK2 phosphorylation. This differential regulation of mGluR5-mediated responses suggests divergent signaling and regulatory pathways which may be important mechanisms for dynamic integration of signal cascades.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Calcium Signaling / physiology
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Enzyme Activators / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Hydrolysis / drug effects
  • Isoenzymes / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Phosphatidylinositols / metabolism*
  • Phospholipase C beta
  • Phosphorylation / drug effects
  • Protein Kinase C / drug effects
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / metabolism*
  • Resorcinols / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Type C Phospholipases / metabolism


  • Enzyme Activators
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Grm5 protein, rat
  • Isoenzymes
  • Phosphatidylinositols
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Resorcinols
  • 3,5-dihydroxyphenylglycine
  • Protein Kinase C
  • Mitogen-Activated Protein Kinase 1
  • Type C Phospholipases
  • Phospholipase C beta
  • Glycine