• The Korean Journal of Physiology and Pharmacology
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• 제7권6호
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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.

• International Journal of Oral Biology
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• 제33권3호
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• pp.97-103
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• 2008

The present study investigated the role of peripheral group I, II, and III metabotropic glutamate receptors (mGluRs) in mustard oil (MO)-induced nociceptive response in the masseter muscles of lightly anesthetized rats. Experiments were carried out on male Sprague-Dawley rats weighing 300-350 gm. After initial anesthesia with sodium pentobarbital (40 mg/kg, i.p.), one femoral vein was cannulated and connected to an infusion pump for intravenous infusion of sodium pentobarbital. The rate of infusion was adjusted to provide a constant level of anesthesia. MO (30 ${\mu}L$) was injected into the mid-region of the left masseter muscle via a 30-gauge needle over 10 seconds. After 30 mL injection of 5, 10, 15, or 20% MO into the masseter muscle, total number of hindpaw-shaking behavior was monitored. Intramuscular administration of MO significantly produced hindpawshaking behavior in a dose-dependent manner, as compared with the vehicle (mineral oil)-treated group. Intramuscular pretreatment with 10 or 100 ng DHPG, a group I mGluRs agonist, enhanced MO-induced hindpaw-shaking behavior, while APDC (20 or 200 ${\mu}g$), a group II mGluRs agonist, or L-AP4 (2 ${\mu}g$), a group III mGluRs agonist, significantly reduced MO-induced nociceptive behavior. The antinociception, produced by group II or III mGluRs agonists, was abolished by pretreatment with LY341495, a group II mGluRs antagonist, or CPPG, a group III mGluRs antagonist, res-pectively. Based on these observations, peripheral mGluRs differentially modulated MO-induced nociceptive behavior response in the craniofacial muscle pain and peripheral group II and III mGluRs agonists could be used in treatment of craniofacial muscle nociception.

• The Korean Journal of Pain
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• 제19권2호
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• pp.131-136
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• 2006

Background: The aim of this study was to clarify the role of spinal groups II and III metabotropic glutamate receptors (mGluRs) with respect to postoperative pain at the spinal level. In addition, the nature of the pharmacological interaction between groups II and III mGluRs agonists and morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. To induce postoperative pain, an incision was made in the plantar surface of the hind paw. A pharmacological characteristic for the interaction between groups II and III mGluRs agonists and morphine was evaluated using a fixed-dose analysis. Results: None of intrathecal group II and III mGluRs agonists modified the withdrawal threshold of the incisional pain. The administration of intrathecal morphine resulted in an increase of a dose dependent withdrawal threshold. A fixed-dose analysis revealed that the group III mGluRs agonist, ACPT-III, increased the antinociceptive action of morphine, while the group II mGluRs agonist, APDC, had no effect the antinociception of morphine. Conclusions: These results suggest that group II and III mGluRs may not play a direct modulatory role in the processing of postoperative pain at the spinal level. However, agonizing group III mGluRs may indirectly contributable to the potentiation of morphines antinociception in the spinal cord. Thus, the combination of morphine and a group III mGluRs agonist may be useful in the management of spinal postoperative pain.

• The Korean Journal of Pain
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• 제18권1호
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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.

• Journal of Microbiology
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• 제42권2호
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• pp.111-116
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• 2004

It is known that Bacillus subtilis glutamyl-tRNA synthetase (GluRS) mischarges E. coli $tRNA_{1}$$^{Gln}$ with glutamate in vitro. It has also been established that the expression of B. subtilis GluRS in Escherichia coli results in the death of the host cell. To ascertain whether E. coli growth inhibition caused by B. subtilis GluRS synthesis is a consequence of Glu-$tRNA_{1}$$^{Gln}$ formation, we constructed an in vivo test system, in which B. subtilis GluRS gene expression is controlled by IPTG. Such a system permits the investigation of factors affecting E. coli growth. Expression of E. coli glutaminyl-tRNA synthetase (GlnRS) also amelio-rated growth inhibition, presumably by competitively preventing $tRNA_{1}$$^{Gln}$ misacylation. However, when amounts of up to 10 mM L-glutamine, the cognate amino acid for acylation of $tRNA_{1}$$^{Gln}$, were added to the growth medium, cell growth was unaffected. Overexpression of the B. subtilis gatCAB gene encoding Glu-$tRNA^{Gln}$ amidotransferase (Glu-AdT) rescued cells from toxic effects caused by the formation of the mis-charging GluRS. This result indicates that B. subtilis Glu-AdT recognizes the mischarged E. coli Glu-$tRNA_{1}$$^{Gln}$, and converts it to the cognate Gln-$tRNA_{1}$$^{Gln}$ species. B. subtilis GluRS-dependent Glu-$tRNA_{1}$$^{Gln}$ formation may cause growth inhibition in the transformed E. coli strain, possibly due to abnormal protein synthesis.

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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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.

• International Journal of Oral Biology
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• 제33권3호
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• pp.83-89
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• 2008

Glutamate-induced cobalt uptake reveals non-NMDA glutamate receptors (GluRs) in rat taste bud cells. Previous studies suggest that glutamate-induced cobalt uptake in taste cells occurs mainly via kainate type GluRs. Cobaltstained cells were immunoreactive against GluR6 and KA1 subunits of GluRs. However, the functions of those type of receptors are not known yet. It is important question which types of taste cells are cobalt-stained when stimulated by glutamate and whether they express these kinds of GluRs. Circumvallate and foliate papilla of Sprague-Dawley rats (45-60 days old) were used. A cobalt-staining technique combined with immunohistochemistry against specific markers for taste bud cell types, such as blood group H antigen (BGH), $\alpha$-gustducin (Gus), or neural cell adhesion molecule (NCAM) was employed. We also performed double labeling of GluR6 or KA1 subunits of GluR with each specific marker for taste bud cell types. Lots of cobaltstained taste bud cells expressed Gus-like immunoreactivity, and subsets of the cobalt stained cells appeared NCAM- or BGH-like immunoreactivity. Stimulation with 1 mM glutamate significantly increased the number of cobaltstained cells in Gus-like immunoreactive cells, but not in NCAM- or BGH-like immunoreactive cells. In the double labeling experiments, GluR6 and KA1 subunits of GluRs were mainly expressed with Gus. These results suggest that kainate glutamate receptors preferentially expressed in type II taste bud cells in rat.

• The Korean Journal of Physiology and Pharmacology
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• 제13권6호
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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 Physiology and Pharmacology
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• 제7권2호
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• pp.53-57
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• 2003

The glutamate receptors (GluRs) are key receptors for modulatory synaptic events in the central nervous system. It has been reported that glutamate increases the intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) and induces cytotoxicity. In the present study, we investigated whether the glutamate-induced $[Ca^{2+}]_i$ increase was associated with the activation of ionotropic (iGluR) and metabotropic GluRs (mGluR) in substantia gelatinosa neurons, using spinal cord slice of juvenile rats (10${\sim}21 day). $[Ca^{2+}]_i$ was measured using conventional imaging techniques, which was combined with whole-cell patch clamp recording by incorporating fura-2 in the patch pipette. At physiological concentration of extracellular $Ca^{2+}$, the inward current and $[Ca^{2+}]_i$ increase were induced by membrane depolarization and application of glutamate. Dose-response relationship with glutamate was observed in both $Ca^{2+}$ signal and inward current. The glutamate-induced $[Ca^{2+}]_i$ increase at holding potential of -70 mV was blocked by CNQX, an AMPA receptor blocker, but not by AP-5, a NMDA receptor blocker. The glutamate-induced $[Ca^{2+}]_i$ increase in $Ca^{2+}$ free condition was not affected by iGluR blockers. A selective mGluR (group I) agonist, RS-3,5-dihydroxyphenylglycine (DHPG), induced $[Ca^{2+}]_i$ increase at holding potential of -70 mV in SG neurons. These findings suggest that the glutamate-induced $[Ca^{2+}]_i$ increase is associated with AMPA-sensitive iGluR and group I mGluR in SG neurons of rats.

• Molecules and Cells
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• 제21권3호
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• pp.418-427
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• 2006

Ionotropic glutamate receptors (iGluRs) are ligand-gated nonselective cation channels that mediate fast excitatory neurotransmission. Although homologues of the iGluRs have been identified in higher plants, their roles are largely unknown. In this work we isolated a full-length cDNA clone (RsGluR) encoding a putative glutamate receptor from small radish. An RsGluR:mGFP fusion protein was localized to the plasma membrane. In Arabidopsis thaliana overexpressing the fulllength cDNA, glutamate treatment triggered greater $Ca^{2+}$ influx in the root cells of transgenic seedlings than in those of the wild type. Transgenic plants exhibited multiple morphological changes such as necrosis at their tips and the margins of developing leaves, dwarf stature with multiple secondary inflorescences, and retarded growth, as previously observed in transgenic Arabidopsis overexpressing AtGluR3.2 [Kim et al. (2001)]. Microarray analysis showed that jasmonic acid (JA)-responsive genes including defensins and JA-biosynthetic genes were up-regulated. RsGluR overexpression also inhibited growth of a necrotic fungal pathogen Botrytis cinerea possibly due to up-regulation of the defensins. Based on these results, we suggest that RsGluR is a glutamate-gated $Ca^{2+}$ channel located in the plasma membrane of higher plants and plays a direct or indirect role in defense against pathogen infection by triggering JA biosynthesis.