Metabotropic glutamate receptor 2 modulates excitatory synaptic transmission in the rat globus pallidus.
While group II metabotropic glutamate receptors (mGluRs) are known to be expressed in the rat globus pallidus (GP), their functions remain poorly understood. We used standard patch clamping technique in GP slices to determine the effect of group II mGluR activation on excitatory transmission in this region. Activation of group II mGluRs with the group-selective agonist DCG-IV or APDC reduced the amplitude of the evoked excitatory postsynaptic currents (EPSCs) and significantly increased the paired pulse ratio suggesting a presynaptic site of action. This was further supported by double-labeling electron microscopy data showing that group II mGluRs (mGluR2 and 3) immunoreactivity is localized in glutamatergic pre-terminal axons and terminals in the GP. Furthermore, we found that LY 487379, an mGluR2-specific allosteric modulator, significantly potentiated the inhibitory effect of DCG-IV on the excitatory transmission in the GP. Co-incubation with 30 microM LY 487379 increased the potency of DCG-IV about 10-fold in the GP. We were thus able to pharmacologically isolate the mGluR2-mediated function in the rat GP using an mGluR2-specific allosteric modulator. Therefore, our findings do not only shed light on the functions of group II mGluRs in the GP, they also illustrate the therapeutic potential of mGluR-targeting allosteric modulators in neurological disorders such as Parkinson's disease.
Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, NE, Atlanta, GA 30329, USA.
Olga
O
Poisik
Dinesh V
DV
Raju
Marc
M
Verreault
Alice
A
Rodriguez
Oluseyi A
OA
Abeniyi
P Jeffrey
PJ
Conn
Yoland
Y
Smith
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D003521:Cyclopropanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D005917:Globus Pallidus / Q000166:cytology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D014966:Xanthenes / Q000494:pharmacology
C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D000596:Amino Acids; D000613:Aminobutyrates; D000779:Anesthetics, Local; D003521:Cyclopropanes; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; C476436:N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl)pyrid-3-ylmethylamine; D011725:Pyridines; D018091:Receptors, AMPA; D013449:Sulfonamides; D014966:Xanthenes; C082313:2-(2,3-dicarboxycyclopropyl)glycine; C012647:QX-314; D008734:Methoxyhydroxyphenylglycol; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D008012:Lidocaine; D011392:Proline; C012729:2-amino-4-phosphonobutyric acid; C104722:glutamate receptor ionotropic, AMPA 2; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol