• The Korean Journal of Physiology and Pharmacology
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• 제5권6호
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• pp.479-485
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• 2001

The existence of opioid receptors in mammalian cerebellum except human, has not been clearly understood. In the present study, we found that NPY was inducible by morphine in the mouse cerebellar granular and Purkinje cell layers. We performed in situ RT-PCR and immunohistochemistry to characterize the NPY expression. The increase of NPY gene expression by morphine (30 mg/kg, i.p.) was inhibited by pretreatment with not only naloxone (100 mg/kg, i.p.) but also a noncompetitive NMDA antagonist, MK-801 (0.3 mg/kg, i.p.). The competitive NMDA antagonist, AP-5 (0.9 mg/kg, i.p.) slightly attenuated the increased NPY expression by morphine. Also, the finding similar to morphine was shown by NMDA (70 mg/kg, i.p.) treatment. Our results indicate that NPY was inducible by morphine and this might reflect activation of NMDA receptors in granule cells that relay mossy fiber inputs to Purkinje cells via parallel fibers.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 춘계학술대회
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• pp.21-37
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• 2003

1. Stimulation of dopaminergic system by morphine was abolished in ${\mu}$-opioid receptor knockout mice. 2. Dopaminergic stimulation by opioid agonists, morphine, DPDPE, and U50488, acts independently. 3. Loss of ${\mu}$-opioid receptors is more sensitive to the response of NMDA-induced convulsion and increase in the expression of mRNA for NMDA receptors.

• Journal of Korean Neurosurgical Society
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• 제29권11호
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• pp.1429-1436
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• 2000

Objectives : This study was performed in cultured rat hippocampal neurons to investigate the acute electrophysiological features of ionotropic glutamate receptors which act as a major excitatory neurotransmitter in mammalian brain. Method : Glutamate receptor agonists were applied into the bath solution embedding in whole-cell patch-clamp recording of single hippocampal neuron. Results : In voltage-clamped at -60mV and the presence of 1mmol $Mg^{2+}$, extracellulary applied NMDA did not induce any inward current. Both the elimination of $Mg^{2+}$ and addition of glycine in bath, however, elicited a NMDAinduced inward current. $Mg^{2+}$ block current was increased gradually in more negative potentials from -30mV, showing a negative slope in I-V plot with $Mg^{2+}$. Glutamate-induced current represented an outward rectification. A non-NMDA receptor component occupied about 40% of glutamate-induced current in the voltage range of -80mV to +60mV. Conclusion : Present study suggests that glutamate activates acutely the non-NMDA receptors which induces an inward current in the level of resting membrane potential. This makes the membrane potential increase and can activate the NMDA receptors that permit calcium influx against $Mg^{2+}$ block. At the depolarized state of neuron, there may be recovery mechanisms of membrane potential to repolarize irrespective of voltage-dependent potassium channels in the hippocampal neurons.

• International Journal of Oral Biology
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• 제32권2호
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• pp.59-65
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• 2007

It has been well known that excitatory amino acids, primarily glutamate, are involved in the transmission of nociception in pathological and physiological conditions in the spinal and brainstem level. Recently, peripheral glutamate also play a critical role in the peripheral nociceptive transmissions. The present study investigated the role of N-methyl-D-aspartic acid (NMDA) or non-NMDA ionotropic glutamate receptors in formalin-induced TMJ pain. Experiments were carried out on male Sprague-Dawley rats weighing 220-280 g. Intra-articular injection was performed under halothane anesthesia. Under anesthesia, AP-7 (10, $100\;{\mu}M$, $1\;mM/20\;{\mu}L$), a NMDA receptor antagonist, or CNQX disodium salt (0.5, 5, 50, $500\;{\mu}M/20\;{\mu}L$), a non-NMDA receptor antagonist, were administered intra-articularly 10 min prior to the application of 5% formalin. For each animal, the number of behavioral responses, such as rubbing and/or scratching the TMJ region, was recorded for nine successive 5-min intervals. Intra-articular pretreatment with 1 mM of AP-7 or $50\;{\mu}M$ CNQX significantly decreased the formalin-induced scratching behavioral responses during the second phase. Intra-articular pretreatment with $500\;{\mu}M$ of CNQX significantly decreased the formalin-induced scratching behavior during both the first and the second phase. These results indicate that the intra-articular administration of NMDA or non-NMDA receptor antagonists inhibit formalin-induced TMJ nociception, and peripheral ionotropic glutamate receptors may play an important role in the TMJ nociception.

• The Korean Journal of Physiology and Pharmacology
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• 제7권2호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제20권4호
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• pp.425-432
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• 2016

In addition to classical synaptic transmission, information is transmitted between cells via the activation of extrasynaptic receptors that generate persistent tonic current in the brain. While growing evidence supports the presence of tonic NMDA current ($I_{NMDA}$) generated by extrasynaptic NMDA receptors (eNMDARs), the functional significance of tonic $I_{NMDA}$ in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate INMDA facilitates the ${\alpha}$-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In $low-Mg^{2+}$ artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in $I_{holding}$ ($I_{GLU}$) at a holding potential ($V_{holding}$) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive $I_{GLU}$ was observed even in normal aCSF at $V_{holding}$ of -40 mV or -20 mV. $I_{GLU}$ was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in $I_{holding}$ ($I_{AMPA}$) in SON MNCs. Pretreatment with AP5 attenuated $I_{AMPA}$ amplitudes to ~60% of the control levels in $low-Mg^{2+}$ aCSF, but not in normal aCSF at $V_{holding}$ of -70 mV. $I_{AMPA}$ attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced $I_{AMPA}$ attenuation in SON MNCs. Finally, chronic dehydration did not affect $I_{AMPA}$ attenuation by AP5 in the neurons. These results suggest that tonic $I_{NMDA}$, mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs.

• The Korean Journal of Physiology and Pharmacology
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• 제27권5호
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• pp.449-456
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• 2023

N-methyl-D-aspartate (NMDA) receptors are ionic glutamine receptors involved in brain development and functions such as learning and memory formation. NMDA receptor inhibition is associated with autophagy activation. In this study, we investigated whether the NMDA receptor antagonists, memantine and ifenprodil, induce autophagy in human retinal pigment epithelial cells (ARPE-19) to remove N-retinylidene-N-retinylethanolamine (A2E), an intracellular lipofuscin component. Fluorometric analysis using labeled A2E (A2E-BDP) and confocal microscopic examination revealed that low concentrations of NMDA receptor antagonists, which did not induce cytotoxicity, significantly reduced A2E accumulation in ARPE-19 cells. In addition, memantine and ifenprodil activated autophagy in ARPE-19 cells as measured by microtubule-associated protein 1A/1B-light chain3-II formation and phosphorylated p62 protein levels. Further, to understand the correlation between memantine- and ifenprodil-mediated A2E degradation and autophagy, autophagy-related 5 (ATG5) was depleted using RNA interference. Memantine and ifenprodil failed to degrade A2E in ARPE-19 cells lacking ATG5. Taken together, our study indicates that the NMDA receptor antagonists, memantine and ifenprodil, can remove A2E accumulated in cells via autophagy activation in ARPE-19 cells.

• 수면정신생리
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• 제7권1호
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• pp.10-17
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• 2000

To investigate the neurobiological bases of learning and memory is one of the ambitious goals of modern neuroscience. The progress in this field of recent years has not only brought us closer to understanding the molecular mechanism underlying long-lasting changes in synaptic strength, but it has also provided further evidence that these mechanisms are required for memory formation. Since twenty years ago, several studies for the tests of the hypothesis that NMDA-dependent hippocampal long-term potentiation(LTP) underlies learning have been reported. Also, in the recent year, data from mutant mice showed that a potential role for NMDA-dependent LTP in hippocampal CA1 and spatial learning. Although the current evidence for the role of NMDA receptor in learning and memory is not still obvious, NMDA receptor seems to act as a critical switch for activation of a cascade of events that underlie synaptic plasticity.

• The Korean Journal of Physiology and Pharmacology
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• 제8권6호
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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 Preventive Medicine and Public Health
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• 제32권4호
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• pp.459-466
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• 1999

Objectives:eurotoxicity is mediated by nitric oxide(NO) in the rat primary neuronal cultures and assess the effect of $Mn^{2+}$ on the N-methyl-D aspartate(NMDA) receptors. Methods: We have used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay to examine the effect of cytotoxicity of $MnCl_2$ in neuronal cells , NO production was determined by measuring nirites, a stable oxidation product of NO. The neurons in the rat that contains neuronal nitric oxide synthase(nNOS) were examined by immunofluorescence and confocal microscopy. The effects of $Mn^{2+}$ on the NMDA receptors was assesed by the whole cell voltage clamp technique. Results: We showed that the NO release and NOS expression was increased with 500uM $MnCl_2$ treatment and an NOS inhibitors, $N^G-nitro-L-arginine$, prevented neurotoxicity elicited by manganese. In the electrophysiological study, $Mn^{2+}$ does not block or activate the NMDA receptors and not pass through the NMDA receptors in a neurons of basal ganglia. Conclusions: It is concluded that manganese neurotoxicity in basal ganglia was partially mediated by nitric oxide in the cell culture model.