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

Peavy RD, Sorensen SD, Conn PJ
J Neurochem. 2002 83 (1): 110-8

PMID: 12358734 · 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.

MeSH Terms (23)

Animals Astrocytes Calcium Signaling Cells, Cultured Enzyme Activation Enzyme Activators Enzyme Inhibitors Excitatory Amino Acid Agonists Glycine Hydrolysis Isoenzymes Mitogen-Activated Protein Kinase 1 Phosphatidylinositols Phospholipase C beta Phosphorylation Protein Kinase C Rats Rats, Sprague-Dawley Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate Resorcinols Signal Transduction Type C Phospholipases

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