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PMID:12514208

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Citation

Poisik, OV, Mannaioni, G, Traynelis, S, Smith, Y and Conn, PJ (2003) Distinct functional roles of the metabotropic glutamate receptors 1 and 5 in the rat globus pallidus. J. Neurosci. 23:122-30

Abstract

Group I metabotropic glutamate receptors (mGluRs) 1 and 5 frequently colocalize in the same neurons throughout the CNS. Because both receptors can couple to the same effector systems, the purpose of their cellular coexpression remains unclear. Here, we report that group I mGluR1 and mGluR5 have distinct functional roles in type II neurons of the rat globus pallidus (GP). Type II GP neurons form a large population of GABAergic projection neurons that are characterized by the presence of inwardly rectifying current I(h), low-threshold voltage-activated calcium current I(t), and activity at rest. Although immunocytochemical analysis reveals a high degree of neuronal colocalization of the two group I mGluRs in the GP, activation of mGluR1 only directly depolarizes type II GP neurons. Interestingly, blockade of mGluR5 by a highly selective antagonist, methylphenylethynylpyridine, leads to the potentiation of the mGluR1-mediated depolarization in this neuronal subpopulation. Metabotropic GluR1 desensitizes during repeated activation with the agonist in type II GP neurons, and blocking mGluR5 prevents the desensitization of the mGluR1-mediated depolarization. Elimination of the activity of protein kinase C (PKC) by an application of 1 microm bisendolylmaleimide or 1 microm chelerythrine, both protein kinase C inhibitors, potentiates the mGluR1-mediated response and prevents the desensitization of mGluR1 in type II GP neurons, suggesting that the effect of mGluR5 on mGluR1 signaling may involve PKC. Together, these data illustrate a novel mechanism by which mGluR1 and mGluR5, members of the same family of G-protein-coupled receptors, can interact to modulate neuronal activity in the rat GP.

Links

PubMed

Keywords

Animals; Cells, Cultured; Central Nervous System/physiology; Electric Conductivity; Enzyme Inhibitors/pharmacology; Excitatory Amino Acid Agonists/pharmacology; Excitatory Amino Acid Antagonists/pharmacology; Globus Pallidus/cytology; Globus Pallidus/physiology; Glycine/analogs & derivatives; Glycine/pharmacology; Neurons/drug effects; Neurons/physiology; Parkinson Disease/drug therapy; Patch-Clamp Techniques; Phenotype; Protein Kinase C/antagonists & inhibitors; Protein Kinase C/physiology; Pyridines/pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate/agonists; Receptors, Metabotropic Glutamate/antagonists & inhibitors; Receptors, Metabotropic Glutamate/physiology; Resorcinols/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:GRM5

enables

GO:0001639: PLC activating G protein-coupled glutamate receptor activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

RAT:GRM5

involved_in

GO:0007268: chemical synaptic transmission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:GRM5

involved_in

GO:0002029: desensitization of G protein-coupled receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:GRM5

involved_in

GO:0007205: protein kinase C-activating G protein-coupled receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:GRM5

involved_in

GO:0007206: phospholipase C-activating G protein-coupled glutamate receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

RAT:GRM1

involved_in

GO:0051899: membrane depolarization

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

RAT:GRM1

involved_in

GO:0051482: positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

RAT:GRM1

involved_in

GO:0007206: phospholipase C-activating G protein-coupled glutamate receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

RAT:GRM1

enables

GO:0001639: PLC activating G protein-coupled glutamate receptor activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete


See also

References

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