• The Korean Journal of Physiology and Pharmacology
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• v.8 no.6
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• pp.301-305
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• 2004

This study examined the effects of N-methyl-D-aspartate (NMDA), ${\alpha}-amino$-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate on basal and electrically-evoked release of acetylcholine (ACh) from the rat hippocampal and striatal slices which were preincubated with $[^3H]choline$. Unexpectedly, the basal and evoked ACh release were not affected at all by the treatment with NMDA $(3{\sim}100{\mu}M)$, AMPA $(1{\sim}100{\mu}M)$ or kainate $(1{\sim}100{\mu}M)$ in hippocampal slices. However, in striatal slices, under the $Mg^{2+}-free$ medium, $30{\mu}M$ NMDA increased the basal ACh release with significant decrease of the electrically-evoked releases. The treatment with $1{\mu}M MK-801 not only reversed the $30{\mu}M$ NMDA-induced decrease of the evoked ACh release, but also attenuated the facilitatory effect of $30\;{\mu}M$ NMDA on the basal ACh release. The treatment with either $30\;{\mu}M$ AMPA or $100\;{\mu}M$ kainate increased the basal ACh release without any effects on the evoked release. The treatment with $10{\mu}M$ NBQX abolished the AMPA- or kainate-induced increase of the basal ACh release. Interestingly, NBQX significantly attenuated the evoked release when it was treated with AMPA, although it did not affect the evoked release alone without AMPA. These observations demonstrate that in hippocampal slices, ionotropic glutamate receptors do not modulate the ACh release in cholinergic terminals, whereas in striatal slices, activations of ionotropic glutamate receptors increase the basal ACh release though NMDA may decrease the electrically-evoked ACh release.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.1022-1026
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• 2005

To clarify the toxic effect on cultured neonatal mouse cerebral neurons damaged by ischemia, we examined the cytotoxicity induced by ischemia and the protective effect of antioxidant and AMPA/kainate receptor antagonist against ischemia-induced cytotoxicity on cultured cerebral neurons. For this study, mice were administrated with 20ug/kg cyclothiazide or 50U/kg vitamin E via intraperitoneal injection for 2 hours before ischemic induction. After cell culture for 7 days, cell viability, amount of neurofilament and protein kinase C activity were examined. Ischemia decreased significantly cell viability, amount of neurofilament and the increase of protein kinase C activity in these cultures. In the protective effect, vitamin I showed remarkably the increase of cell viability and amount of neurofilament, and the decrease of protein kinase C activity but, cyclothiazide did not showed any protective effect on ischemia-induced cytotoxicity. From these results, it is suggested that vitamin I is effective in blocking the neurotoxicity induced by ischemia, but cyclothiazide as a AMPA/kainate receptor antagonist is not.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.613-617
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• 2001

The present study examined the hypothesis that NMDA, AMPA/Kainate, and metabotropic (mGlu) glutamate receptors contribute to a behavioral stimulation induced by activation of dopamine receptors by comparing responses in apomorphine-induced cage climbing behaviors in mice. MK-801, CNQX, and MCPG were served as the NMDA receptor, AMPA/Kainate receptor, and mGlu receptor antagonist, respectively, to elucidate the glutamatergic modulation in apomorphine-induced eopaminergic activation in mice. Drugs were administered intracerebroventricularly (i.c.v.) into the mouse brain 15 min before the apomorphine treatment (2 mg/kg, s.c.). 1.c.v. injection of MK-801 inhibited the apomorphine-induced cage climbing behavior dose-dependently. However, treatments with CNQX and MCPG did not any significant change in apomorphine-induced cage climbing behavior in mice. These results suggest that stimulation of NMDA type of glutamate receptors could contribute to the dopaminergic sti mutation, but not AMPA/Kainate and mGlu type glutamate receptors.

• 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 Pain
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• v.13 no.1
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• pp.8-18
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• 2000

Background: Intraperitoneal (IP) and intrathecal (IT) administration of $\alpha$-amino-3-hydroxy-5-methyl-4-isoxazole-propionic (AMPA) and kainate (KA) receptor antagonist attenuate hyperalgesia in various models of persistent pain. The purpose of this study was to assess the effects of IP and IT LY293558, a novel AMPA/KA receptor antagonist on mechanical hyperalgesia after incision. Methods: Sprague-Dawley rats were anesthetized with halothane and underwent plantar incision. Two hours later, responses to mechanical stimuli were assessed using the response frequency to a nonpunctate mechanical stimulus and withdrawal threshold to calibrated von Frey filaments. One group of rats received vehicle, 5 or 10 mg/kg of LY293558 IP. In the other group, vehicle, 0.2, 0.5 or 2 nmol of LY293558 was administered IT. Ataxia and motor function were also evaluated. Results: Hyperalgesia was persistent in both the vehicle and 5 mg/kg group. IP administration of 10 mg/kg of LY293558 increased withdrawal threshold at 30 and 60 min after incision; deficits in rotorod performance were observed at 30, 60, 90 and 150 min. IT administration of 0.5 nmol of LY293558 increased the median withdrawal threshold at 30 and 60 min. Motor function was only impaired at 30 min. IT administration of 2 nmol produced hemiparesis. Again, inhibition of pain behaviors outlasted the effects on motor function. Conclusions: These data further suggest AMPA/KA receptors are important for the maintenance of pain behaviors caused by incisions. IT administration of LY293558 was more effective than systemic administration and reducing pain behaviors caused by a surgical incision.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.141-144
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• 1995

Serotonergic neurons in brainstem play important roles in the endogenous descending pain inhibitory system. To illucidate the involvement of glutamate receptors in the regulation of brainstem serotonergic neurons, we studied the effects of glutamate receptor agonists on 5-hydroxytryptamine(5-HT) release from cultured neurons of rat fetal (gestational age 14th day) brainstem. Cultured cells maintained for 10 days in vitro were stimulated for 30 minutes with agonists of glutamate receptor subtypes at 10-1,000 micromolar concentration. Glutamate (10-1,000 M) increased 5-HT release in a concentration-dependent manner. N-methyl-D-aspartic acid $(NMDA)(10-1,000\;{\mu}M)$ increased 5-HT release in a concentration-dependent manner. Non-NMDA receptor agonists, kainate and $AMPA(3-1,000\;{\mu}M)$ also concentration-dependently increased 5-HT release. These results suggest that both NMDA and non-NMDA receptors regulate 5-HT release from brainstem serotonergic neurons.

• Journal of Korean Ophthalmic Optics Society
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• v.19 no.3
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• pp.413-418
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• 2014

Purpose: The objective of this study was analyzing the distribution of the excitatory neurotransmitter glutamate receptor to investigate the function in the retina of the greater horseshoe bat. Methods: After retinal tissues of adult greater horseshoe bat were cut into $40{\mu}m$ vertical sections, standard immuno-cytochemical techniques was applied for analysis. Immunofluorescence images were obtained using the Bio-Rad MRC 1024 laser scanning confocal microscope. Results: AMPA (GluR1-4), Kainate (GluR5-7, KA1-2) and NMDA (1, 2A, 2B) mainly distributed in the inner plexiform layer and outer plexiform layer. KA1 receptors have existed not only plexiform layer but also ganglion cell layer. Conclusions: The greater horseshoe bat has same neuron and neurotransmitter to mammalian retina. These findings suggest that bat has a functional retina for visual analysis.

• Proceedings of the Botanical Society of Korea Conference
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• 2001.04a
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• pp.11-11
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• 2001

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.996-1001
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• 2003

It is well known that oxidative stress of reactive oxygen species(ROS) may be a causative factor in the pathogenesis of bone disorder. The purpose of this study was to evaluate the cytotoxicity of oxidative stress. Cell viability by MTS assay or INT assay, activity of glutathione peroxidase(GPx), lipid peroxidation(LPO) activity and cell viablity. And also protctive effect of glutamate receptors against ROS-induced osteotoxicity was examined by protein synthesis, alkaline phosphatase (ALP) activity and lactate dehydrogenase (LDH) activity in cultured rat osteoblasts and osteoclasts. XO/HX decreased cell viability and GPx activity, protein synthesis and ALP activity, but increased LPO activity and LDH activity. In the protective effect, N-methyl-D-aspartate (NMDA) receptor antagonists or AMPA/kainate receptor antagonists such as D-2-amino-5-phosphonovaleric acid (APV), 7-chlorokynurenic acid (CKA), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX), NMDA receptor antagonists but AMPA/kainate receptor antagonists showed protective effect on xanthine oxidase (XO) and hypoxanthine (HX) in these cultures by the increse of protein synthesis, ALP activity.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.2
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• pp.59-63
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• 2003

The medial vestibular nucleus (MVN) neurons are controlled by excitatory synaptic transmission from the vestibular afferent and commissural projections, and by inhibitory transmission from interneurons. Spontaneous synaptic currents of MVN neurons were studied using whole cell patch clamp recording in slices prepared from 13- to 17-day-old rats. The spontaneous inhibitory postsynaptic currents (sIPSCs) were significantly reduced by the $GABA_A$ antagonist bicuculline ($20{\mu}M$), but were not affected by the glycine antagonist strychnine ($1{\mu}M$). The frequency, amplitude, and decay time constant of sIPSCs were $4.3{\pm}0.9$ Hz, $18.1{\pm}2.0$ pA, and $8.9{\pm}0.4$ ms, respectively. Spontaneous excitatory postsynaptic currents (sEPSCs) were mediated by non-NMDA and NMDA receptors. The specific AMPA receptor antagonist GYKI-52466 ($50{\mu}M$) completely blocked the non-NMDA mediated sEPSCs, indicating that they are mediated by an AMPA-preferring receptor. The AMPA mediated sEPSCs were characterized by low frequency ($1.5{\pm}0.4$ Hz), small amplitude ($13.9{\pm}1.9$ pA), and rapid decay kinetics ($2.8{\pm}0.2$ ms). The majority (15/21) displayed linear I-V relationships, suggesting the presence of GluR2-containing AMPA receptors. Only 35% of recorded MVN neurons showed NMDA mediated currents, which were characterized by small amplitude and low frequency. These results suggest that the MVN neurons receive excitatory inputs mediated by AMPA, but not kainate, and NMDA receptors, and inhibitory transmission mediated by $GABA_A$ receptors in neonatal rats.