• 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.

• 동의생리병리학회지
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• 제19권4호
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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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• 제24권6호
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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.

• 생명과학회지
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• 제15권3호
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• pp.505-512
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• 2005

신경흥분독성과 간질발작발현은 glutamate 수용체활성과 연관이 있다고 알려져 있다. a-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), kainate 수용체에 대한 glutamate 활성을 포함하는 다양한 기전을 가진 항전간제인 Topiramate는 신경보호작용을 가진다는 증거가 제시되어 Topiramate가 간질발작 후 해마의 glutamate 수용체 발현에 미치는 효과를 관찰하였다. 흰쥐에 kainate를 복강 내 주사하여 간질중첩증을 유발시킨 후 Topiramate를 1주일 주사하였다 Apop tag in situ detection kit를 이용하여 세포손상을 관찰한 결과 kainate 유발 간질중첩증 1주일 후 해마의 CA1, CA3에서 심각한 세포사를 보였으나, Topiramte 처리 군에서는 세포사가 현저히 감소하였다. 간질중첩증 이후 NMDA 수용체 아형 1,2a, 2b 발현이 현저히 증가했으나 Topiramate 처치에 의해 NMDA수용체의 발현에는 뚜렷한 변화가 없었다. AMPA수용체에서는 GluR1이 간질중첩증 이후 현저히 상향 조정되었고 GluR2는 현저히 하향조정 되었다 Topiramate 1주일 처리 시 간질중첩증으로 인해 변화된 CluR1과 GluR2의 발현이 역전되었다. 결론적으로 Topiramate는 간질중침증에 의한 CluR1/CluR2 발현비의 증가로 유발되는 흥분성 신경세포사를 억제시킴으로써 신경보호작용이 있는 것으로 보인다.

• The Korean Journal of Pain
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• 제13권1호
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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.

• 대한약리학회지
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• 제31권2호
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• pp.141-144
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• 1995

뇌간의 세로트닌 신경계는 내재성 하행성 동통억제계(endogenous descending pain inhibitory system)에 있어서 중추적인 역할을 하고 있다. 뇌간의 세로토닌 신경세포에 대한 glutamate 수용체 중 N-methyl-D-aspartic acid-(NMDA-) 및 non-NMDA 수용체 효현제들의 작용을 알아보기 위하여, 쥐의 태자(태생 14일)로부터 뇌간을 분리하여 10일 동안 배양한 후 5-hydroxytryptamine(5-HT)의 분비에 대한 각 glutamate 수용체 효현제들이 영향을 연구하였다. Glutamate를 $10\;{\mu}M$에서 $1000\;{\mu}M$까지 농도를 변화하여 30분 동안 배지에 가한 후, 배지내에 분비되는 세로토닌을 측정한 결과, 농도 의존적으로 세로토닌의 분비가 증가되었다. Glutamate 수용체 중에서 NMDA 수용체 효현제인 NMDA를 $10\;{\mu}M$에서 $1000\;{\mu}M$까지 농도를 변화하여 30분 동안 배지에 가한 후, 배지내에 분비되는 세로토닌을 측정한 결과, 농도 의존적으로 세로토닌의 분비가 증가되었다. Non-NMDA 수용체 효현제인 kainate 및 AMPA를 $3\;{\mu}M$에서 $300\;{\mu}M$까지 농도를 변화하여 배지에 처리한 결과, 각 효현제에 의해 농도 의존적으로 세로토닌의 분비가 증가됨을 관찰하였다. 이상의 연구결과, 쥐의 태자(태생 14일)로부터 분리하여 10일동안 배양한 뇌간의 세로토닌 신경세포에 있어서 glutamate, NMDA, kainate 및 AMPA 모두 5-HT의 분비를 자극함으로써, NMDA- 및 non-NMDA 수용체 모두 5-HT의 분비에 관여하고 있음을 나타낸다.

• 한국안광학회지
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• 제19권3호
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• pp.413-418
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• 2014

목적: 한국관박쥐 망막의 기능을 알아보기 위해서 흥분성 신경전달물질인 글루타메이트 수용체의 분포도를 분석하였다. 방법: 성체 한국관 박쥐의 망막을 $40{\mu}m$ 수직 절편 한 후 표준면역세포화학법을 이용하였다. 면역형광이미지는 Bio-Rad MRC 1024 공초점 현미경을 사용하여 얻었다. 결과: AMPA (GluR1-4), Kainate (GluR5-7, KA1-2), NMDA (1, 2A, 2B)는 내망상층과 외망상층에 주로 분포되어 있었다. KA1은 신경절세포층에도 많은 수의 수용체가 존재하였다. 결론: 한국관박쥐는 포유류망막에 있는 신경세포와 신경전달물질을 동일하게 가지고 있었다. 한국관박쥐도 기능적 망막을 가지고 있음을 제시한다.

• 한국식물학회:학술대회논문집
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• 한국식물학회 2001년도 춘계학술발표대회:발표눈문요지록
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• pp.11-11
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• 2001

• 동의생리병리학회지
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• 제17권4호
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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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• 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.