• Molecules and Cells
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• v.21 no.1
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• pp.34-41
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• 2006

The neuronal localization of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor (GluR) subunits is vital as they play key roles in the regulation of calcium permeability. We have examined the distribution of the calcium permeable AMPA glutamate receptor subunit GluR1 in the mouse visual cortex immunocytochemically. We compared this distribution to that of the calcium-binding proteins calbindin D28K, calretinin, and parvalbumin, and of GABA. The highest density of GluR1-immunoreactive (IR) neurons was found in layers II/III. Enucleation appeared to have no effect on the distribution of GluR1-IR neurons. The labeled neurons varied in morphology; the majority were round or oval and no pyramidal cells were labeled by the antibody. Two-color immunofluorescence revealed that 26.27%, 10.65%, and 40.31% of the GluR1-IR cells also contained, respectively, calbindin D28K, calretinin, and parvalbumin. 20.74% of the GluR1-IR neurons also expressed GABA. These results indicate that many neurons that express calcium-permeable GluR1 also express calcium binding proteins. They also demonstrate that one fifth of the GluR1-IR neurons in the mouse visual cortex are GABAergic interneurons.

• Journal of Life Science
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• v.20 no.1
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• pp.1-8
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• 2010

We recently reported the distributions of AMPA ($\alpha$-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) receptor subtypes glutamate receptors (GluR) 1 and GluR4 in the superior colliculi (SC) of hamsters with antibody immunocytochemistry and the effect of enucleation on these distributions. We also compared these labelings to those of calcium-binding proteins calbindin D28K, calretinin, parvalbumin, and GABA. In the present study, we investigated whether the GluR1- and GluR4-immunoreactive (IR) neurons are interneurons or projection neurons by injection of the retrograde tracer horseradish peroxidase (HRP) into one of each major ascending and descending pathways of the SC. HRP injections were made into a tecto-reticulospinal pathway (TRS) and dorsal lateral geniculate nucleus (dLGN). Animals were then allowed to recover and to survive for 48 hr before perfusion. Sections containing retrograde-labeled neurons were then treated for GluR-immunoreactivity. HRP injections proved that only a small population of the GluR1-IR cells project into TRS (1.4%) and dLGN (2.6%). However, a large subpopulation of GluR4-IR cells project into TRS (32.7%). The differential compositions of inter/projection neurons, along with our previous studies on the separate distribution of the GluR subunits, its differential co-localization with calcium-binding proteins and GABA, and differential reactions to enucleations, strongly imply the functional variety of the receptor subunits in visual behavior responses.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.2
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• pp.95-100
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• 2011

DREAM (downstream regulatory element antagonistic modulator) is a calcium-binding protein that regulates dynorphin expression, promotes potassium channel surface expression, and enhances presenilin processing in an expression level-dependent manner. However, no molecular mechanism has yet explained how protein levels of DREAM are regulated. Here we identified group I mGluR (mGluR1/5) as a positive regulator of DREAM protein expression. Overexpression of mGluR1/5 increased the cellular level of DREAM. Up-regulation of DREAM resulted in increased DREAM protein in both the nucleus and cytoplasm, where the protein acts as a transcriptional repressor and a modulator of its interacting proteins, respectively. DHPG (3,5-dihydroxyphenylglycine), a group I mGluR agonist, also up-regulated DREAM expression in cortical neurons. These results suggest that group I mGluR is the first identified receptor that may regulate DREAM activity in neurons.

• International Journal of Oral Biology
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• v.36 no.2
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• pp.71-78
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• 2011

Using whole cell current- and voltage-clamp recording we investigated the characteristics and pharmacology of group I metabotropic glutamate receptor (mGluR)-mediated responses in rat medial vestibular nucleus (MVN) neurons. In current clamp conditions, activation of mGluR I by application of the group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) induced a direct excitation of MVN neurons that is characterized by depolarization and increased spontaneous firing frequency. To identify which of mGluR subtypes are responsible for the various actions of DHPG in MVN, we used two subtype-selective antagonists. (S)-(+)- alpha-amino-a-methylbenzeneacetic acid (LY367385) is a potent competitive antagonist that is selective for mGluR1, whereas 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is a potent noncompetitive antagonist that is selective for mGluR5. In voltage clamp conditions, DHPG application increased the frequency of spontaneous and miniature inhibitory postsynaptic currents (IPSCs) but had no effect on amplitude distributions. Antagonism of the DHPG-induced increase of miniature IPSCs required the blockade of both mGluR1 and mGluR5. DHPG application induced an inward current, which can be enhanced under depolarized conditions. DHPG-induced current was blocked by LY367385, but not by MPEP. Both LY367385 and MPEP antagonized the DHPG-induced suppression of the calcium activated potassium current ($I_{AHP}$). These data suggest that mGluR1 and mGluR5 have similar roles in the regulation of the excitability of MVN neurons, and show a little distinct. Furthermore, mGluR I, via pre- and postsynaptic actions, have the potential to modulate the functions of the MVN.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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• pp.237-243
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• 2008

Intraplantar injection of melittin has been known to induce sustained decrease of mechanical threshold and increase of spontaneous flinchings. The present study was undertaken to investigate how the melittin-induced nociceptive responses were modulated by changes of metabotropic glutamate receptor (mGluR) activity. Changes in paw withdrawal threshold (PWT), number of flinchings and paw thickness were measured at a given time point after injection of melittin ($10{\mu}g$/paw) into the mid-plantar area of rat hindpaw. To observe the effects of mGluRs on the melittin-induced nociceptions, group I mGluR (AIDA, $100{\mu}g$ and $200{\mu}g$), $mGluR_1$ (LY367385, $50{\mu}g$ and $100{\mu}g$) and $mGluR_5$ (MPEP, $200{\mu}g$ and $300{\mu}g$) antagonists, group II (APDC, $100{\mu}g$ and $200{\mu}g$) and III (L-SOP, $100{\mu}g$ and $200{\mu}g$) agonists were intrathecally administered 20 min before melittin injection. Intraplantar injection of melittin induced a sustained decrease of mechanical threshold, spontaneous flinchings and edema. The effects of melittin to reduce mechanical threshold and to induce spontaneous flinchings were significantly suppressed following intrathecal pre-administration of group I mGluR, $mGluR_1$ and $mGluR_5$ antagonists, group II and III mGluR agonists. Group I mGluR antagonists and group II and III mGluR agonists had no significant effect on melittin-induced edema. These experimental findings indicate that multiple spinal mGluRs are involved in the modulation of melittin-induced nociceptive responses.

• Journal of Life Science
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• v.15 no.3 s.70
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• pp.505-512
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• 2005

Excitotoxicity and epileptogenesis have often been associated with glutamate receptor activation. Accumulating evidences indicates that topiramate (TPM), an antiepileptic drug with multiple mechanisms of action has neuroprotective activity. We explored the neuroprotective effect of TPM on the status epilepticus (SE)-induced hippocampal neuronal death. After development of SE by kainite injection (15 mg/Kg), rats were treated with TPM (10mg/kg) for 1 week. The neuronal death was detected by Apop tag in situ detection kit, and the expression levels of glutamate receptors were semi-quantitatively analyzed by immunoblot. Kainate-induced SE caused a significant neuronal death and cell loss in CAI and CA3 regions of hippocampus at 1 week. However, treatment of TPM for 1 week after SE markedly reduced hippocampal neuronal death. The expression of N-methyl-D-aspartate (NMDA) receptor subunit 1, was increased by SE, but was not affected by 1 week treatment of TPM. The expressions of NMDA receptor subunit 2a and 2b were not changed by either SE or TPM. As for ${\alpha}-amino-3-hydroxy-5-methyl-4-isoxazole-propionate$ (AMPA) glutamate receptors (GluR), kainate-induced SE markedly up-regulated GluR1 expression but down-regulated GluR2 expression, leading to increased formation of $Ca^{2+}$ permeable GluR2- lacking AMPA receptors. TPM administration for 1 week attenuated SE-induced expression of both the up-regulation of GluR1 and down-regulation of GluR2, reversing the ratio of GluR1/GluR2 to the control value. In conclusion, TPM protects neuronal cell death against glutamate induced excitotoxicity in kainate-induced SE model, supporting the potential of TPM as a neuroprotective agent.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.303-306
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• 2003

Metabotropic glutamate receptors (mGluRs), classified into three groups (group I, II, III), play a critical role in modulation of synaptic transmission at central and peripheral synapses. In the present study, extracellular field potential recording techniques were used to investigate effects of mGluR agonists on excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala. The non-selective mGluR agonist t-ACPD ($100{\mu}M$) produced reversible, short-term depression, but the group III mGluR agonist L-AP4 ($50{\mu}M$) did not have any significant effects on amygdala synaptic transmission, suggesting that group I and/or II mGluRs are involved in the modulation by t-ACPD. The group I mGluR agonist DHPG ($100{\mu}M$) produced reversible inhibition as did t-ACPD. Unexpectedly, the group II mGluR agonist LCCG-1 ($10{\mu}M$) induced long-term as well as short-term depression. Thus, our data suggest that activation of group I or II mGluRs produces short-term, reversible depression of excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala. Considering the long-term effect upon activation of group II mGluRs, lack of long-term effects upon activation of group I and II mGluRs may indicate a possible cross-talk among different groups of mGluRs.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.557-564
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• 2016

Metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD), a type of synaptic plasticity, is characterized by a reduction in the synaptic response, mainly at the excitatory synapses of the neurons. The hippocampus and the cerebellum have been the most extensively studied regions in mGluR-dependent LTD, and Group 1 mGluR has been reported to be mainly involved in this synaptic LTD at excitatory synapses. However, mGluR-dependent LTD in other brain regions may be involved in the specific behaviors or diseases. In this paper, we focus on five cortical regions and review the literature that implicates their contribution to the pathogenesis of several behaviors and specific conditions associated with mGluR-dependent LTD.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.455-460
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• 2009

Glutamate-induced cobalt uptake reveals that non-NMDA glutamate receptors (GluRs) are present in rat taste bud cells. Previous studies involving glutamate induced cobalt staining suggest this uptake mainly occurs via kainate type GluRs. It is not known which of the 4 types of taste bud cells express subunits of kainate GluR. Circumvallate and foliate papillae of Sprague-Dawley rats (45~60 days old) were used to search for the mRNAs of subunits of non-NMDA GluRs using RT-PCR with specific primers for GluR1-7, KA1 and KA2. We also performed RT-PCR for GluR5, KA1, $PLC\beta2$, and NCAM/SNAP 25 in isolated single cells from taste buds. Taste epithelium, including circumvallate or foliate papilla, express mRNAs of GluR5 and KA1. However, non-taste tongue epithelium expresses no subunits of non-NMDA GluRs. Isolated single cell RT-PCR reveals that the mRNAs of GluR5 and KA1 are preferentially expressed in Type II and Type III cells over Type I cells.

• The Korean Journal of Pain
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• v.18 no.1
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• pp.1-9
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• 2005

Background: Spinal metabotropic glutamate receptors (mGluRs) and opioid receptors are involved in the modulation of nociception. Although opioid receptors agonists are active for pain, the effects of the compounds for the mGluRs have not been definitely investigated at the spinal level. We examined the effects of the intrathecal mGluR compounds and morphine in the nociceptive test, and then we further clarified the role of the spinal mGluRs. In addition, the nature of the pharmacological interaction after the coadministration of mGluRs compounds with morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. For the induction of pain, $50{\mu}l$ of 5% formalin solution or a thermal stimulus was applied to the hindpaw. An isobolographic analysis was used for the evaluation of the drug interaction. Results: Neither group I mGluR compounds nor group III mGluR compounds produced any antinociceptive effect in the formalin test. The group II mGluR agonist (APDC) had little effect on the formalin-induced nociception. The group II mGluR antagonist (LY 341495) caused a dose-dependent suppression of the phase 2 flinching response on the formalin test, but it did not reduce the phase 1 response of the formalin test nor did it increase the withdrawal latency of the thermal stimulus. Isobolographic analysis revealed a synergistic interaction after the intrathecal delivery of a LY 341495-morphine mixture. Conclusions: These results suggest that group II mGluRs are involved in the facilitated processing at the spinal level, and the combination of LY 341495 with morphine may be useful to manage the facilitated pain state.