• 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.

• Journal of Acupuncture Research
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• 제17권4호
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• pp.5-17
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• 2000

To research the characteristics of ion currents induced by Bujaijung-tang and Bojungikgi-tang, nystatin-perforated patch clamp technique under voltage-c(amp condition was used. Periaqueductal gray neuron was dissociated from Sprauge-Dawley rat, 10-15 days old. Cytotoxicity of Bujaijung-tang and Bojungikgi-tang showed incubation time and concentration dependent manner. Ion current activated by Bujaijung-tang and Bojungikgi-tang were inhibited by bicuculline and strychnine and CNQX. It can be suggested that Bujaijung-tang and Bojungikgi-tang modulate inhibitory and excitatory neurotransmitters-, GABA, glycine and non-NMDA, acticvated ion channels. Modulatory effect of Bujaijung-tang and Bojungikgi-tang was more greater in inhibitory neurotransmitters. Low concentration of Bujaijung-tang which dose not elicit ion current itself, activated GABA and glycine induced chloride currents. In this study, we can found that the activation of Bujaijung-tang and Bojungikgi-tang on non-NMDA subtypes of glutamate receptor is its major action mechanism and can be used as very effective Herb treatment on Myasthenia gravis patient.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.143-143
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• 1998

Antagonists acting at the glycine site of the NMDA receptor have been gaining safer alternatives for stroke therapy because they have few adverse effect competitive and noncompetitive NMDA antagonists. Therefore, the neuroprotect novel glycine site antagonist KC0244 were evaluated in a rat model of transient comparison with GV150526A in a developmental phase. Middle cerebral artery oc was produced by insertion of a silicone-coated 4-0 nylon monofilament to the o in male Sprague-Dawley rats under isoflurane anesthesia. After 90 or 120 min retracted and the ischemic tissue reperfused. In 90-min MCAO model, GV150526A was administered 30 min before MCAO or immediately after MCAO. In 120-min MC KC0244 or GV150526A (10 mg/kg, i.p.) was administered 1 hr before MCAO or imme MCAO. Infarct volume was measured 24 hr after MCAO using the 2,3,5-triphe chloride staining method. In 90-min MCAO model, treatments with GV1505 significantly reduce infarct volume although they tended to slightly reduce cor approximately 19% compared with the nontreated group. In 120-min MCAO model with GV150526A did not either significantly reduce infarct volume although the reduce total infarct volume by approximately 16% compared with the vehicle-tre However, 1-hr preischemic and immediate treatments with KC0244 reduced total i 39 and 30% (corrected total infarct volume by 44 and 32%), respectively, co vehicle-treated control group. The results suggest that KC0244 can provid against transient focal ischemic damage with greater in vivo potency than GV150

• Tuberculosis and Respiratory Diseases
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• 제45권1호
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• pp.77-89
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• 1998

서 론: $\beta_2$ 교감신경 수용체 유전자에는 여러 종류의 다형성(polymorphism)가 존재하며, 천식 환자에서 $\beta_2$ 교감신경 수용체의 대표적인 변이는 $\beta_2$ 교감신경 수용체의 아미노산이 대치된 부분으로 Arg16-Gly, Gln27-Glu, Val34-Met 및 Thr164-Ile 등인 것으로 알려져 있다. 지속적인 $\beta_2$ 교감신경 유도체의 자극에 대하여 세포표면으로 부터 세포내의 전달과정이 둔화되어 점차 세포전달이 없어질 수도 있는 desensitization 또는 수용체와 수가 감소하는 downregulation이 존재하는 것으로 알려져 있다. 천식환자에서 $\beta_2$ 교감신경 수용체의 desensitization 또는 downregulation 뿐만 아니라 천식 표현형과 $\beta_2$ 교감신경 수용체 유전자 다형성의 상관 관계에 대한 연구가 이루어지고 있으나 논란이 많다. 이에 본 연구는 기관지 천식환자에서 $\beta_2$ 교감신경 수용체의 가장 흔한 16, 27, 34 및 164 의 아미노산에 해당하는 유전자의 다형성을 MASA (Mutated Allele Specific Amplification)법으로 시행하여 각각의 다형성의 발생 빈도와 천식의 심한 정도와 연관이 있는 가를 확인하였다. 대상 및 방법: 대상 환자는 천식 환자 103명이었으며, 이중 남자는 54명, 여자는 49명으로 평균 연령은 46.6세 (19~80세)였고 이환 기간은 4.7년이었다. 대상 환자는 경미하고 간헐적 증상을 보인 30명, 지속적인 경미한 천식 환자는 32명으로 경미한 천식은 모두 62명이었으며, 중등증의 천식 증상은 17명 및 중종의 천식증상을 보인 환자는 24명이었다. 이중 1년 중에 6개월 이상 전신적 스테로이드를 투여하는 환자는 39명이었으며, 투약 중에도 야간 발작이나 야간 기침이 발생되었던 환자는 44명이었다. 대상 환자로부터 10cc의 전혈구를 체취 하여 분리된 림파구에서 분리된 DNA를 이용하여 MASA 방법으로 $\beta_2$ 교감신경 수용체 16번, 27번, 34번 및 164번째 아미노산의 다형성을 검색하였고, 천식의 심한 정도 따른 $\beta_2$ 교감신경 수용체 유전자의 다형성의 분포와 야간 천식의 발작이나 증상의 유무에 따른 $\beta_2$ 교감신경 수용체 유전자의 다형성의 분포를 확인하였다. 결 과: 16 번째 Arginine이 Glycine으로 변이는 heterozygous 변이가 67명, homozygous 변이가 13명으로 heterozygous 변이가 65.1%로 가장 많았다. 27번째 Glutamine이 Glutamate로 변이는 heterozygous만 11명으로 10.7%였으며, 34번째 Valine이 Methionine으로 변이를 일으키는 100번째 핵산의 경우도 heterozygous만 6명으로 5.8%였다. 27 번째와 34번째 아미노산의 변이를 일으키는 homozygous 변이와 164번째 아미노산의 변이는 대상 환자 중에는 없었다. 천식 증상의 심한 정도를 경종 및 중등증, 중중으로 2 구분하여 $\beta_2$ 교감신경 수용체 다형성의 발생빈도를 관찰한 결과 중증의 천식환자에서 16번째 아미노산의 변이의 빈도는 많았으나 (p=0.015), 27번, 34번 및 164번째의 아미노산의 변이는 천식 증상의 정도와는 연관성이 없었다. 야간 천식 증상의 유무에 따른 $\beta_2$ 교감신경 수용체 다형성은 16, 27, 34 및 164번째 아미노산의 핵산의 변이와 연관성이 없었다. 결 론: 이상의 결과로 기관지 천식 환자에서 $\beta_2$ 교감신경 수용체 다형성은 Arg 16, Gln 27 및 Val 34의 변이가 존재하고, Arg 16이 가장 많았으며, Thr 164는 없었다. 기관지 천식 환자에서 증상이 심한 중증 천식은 $\beta_2$ 교감 신경 수용체의 다형성중 Arg 16의 변이는 중증 천식과 연관성이 있었다. 그러나 야간 천식 발작이나 증상과 $\beta_2$ 교감신경 수용체 다형성은 서로 상관이 없었다.

• The Korean Journal of Physiology and Pharmacology
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• 제15권1호
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• pp.17-22
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• 2011

Quercetin mainly exists in the skin of colored fruits and vegetables as one of flavonoids. Recent studies show that quercetin, like other flavonoids, has diverse pharmacological actions. However, relatively little is known about quercetin effects in the regulations of ligand-gated ion channels. In the previous reports, we have shown that quercetin regulates subsets of homomeric ligand-gated ion channels such as glycine, 5-$HT_{3A}$ and ${\alpha}7$ nicotinic acetylcholine receptors. In the present study, we examined quercetin effects on heteromeric neuronal ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor channel activity expressed in Xenopus oocytes after injection of cRNA encoding bovine neuronal ${\alpha}3$ and ${\beta}4$ subunits. Treatment with acetylcholine elicited an inward peak current ($I_{ACh}$) in oocytes expressing ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor. Co-treatment with quercetin and acetylcholine inhibited $I_{ACh}$ in oocytes expressing ${\alpha}3{\beta}4$ nicotinic acetylcholine receptors. The inhibition of $I_{ACh}$ by quercetin was reversible and concentration-dependent. The half-inhibitory concentration ($IC_{50}$) of quercetin was $14.9{\pm}0.8\;{\mu}M$ in oocytes expressing ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor. The inhibition of $I_{ACh}$ by quercetin was voltage-independent and non-competitive. These results indicate that quercetin might regulate ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor and this regulation might be one of the pharmacological actions of quercetin in nervous systems.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2008년도 추계학술발표회
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• pp.388-389
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• 2008

• The Korean Journal of Physiology and Pharmacology
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• 제26권6호
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• pp.531-540
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• 2022

Group 1 metabotropic glutamate receptors (mGluRs) can positively affect postsynaptic neuronal excitability and epileptogenesis. The objective of the present study was to determine whether group 1 mGluRs might be involved in synaptically-induced intracellular free Ca²⁺ concentration ([Ca²⁺]_i) spikes and neuronal cell death induced by 0.1 mM Mg²⁺ and 10 µM glycine in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague-Dawley rats using imaging methods for Ca²⁺ and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for cell survival. Reduction of extracellular Mg²⁺ concentration ([Mg²⁺]_o) to 0.1 mM induced repetitive [Ca²⁺]_i spikes within 30 sec at day 11.5. The mGluR5 antagonist 6-Methyl2-(phenylethynyl) pyridine (MPEP) almost completely inhibited the [Ca²⁺]_i spikes, but the mGluR1 antagonist LY367385 did not. The group 1 mGluRs agonist, 3,5-dihydroxyphenylglycine (DHPG), significantly increased the [Ca²⁺]_i spikes. The phospholipase C inhibitor U73122 significantly inhibited the [Ca²⁺]_i spikes in the absence or presence of DHPG. The IP₃ receptor antagonist 2-aminoethoxydiphenyl borate or the ryanodine receptor antagonist 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate also significantly inhibited the [Ca²⁺]_i spikes in the absence or presence of DHPG. The TRPC channel inhibitors SKF96365 and flufenamic acid significantly inhibited the [Ca²⁺]_i spikes in the absence or presence of DHPG. The mGluR5 antagonist MPEP significantly increased the neuronal cell survival, but mGluR1 antagonist LY367385 did not. These results suggest a possibility that mGluR5 is involved in synaptically-induced [Ca²⁺]_i spikes and neuronal cell death in cultured rat hippocampal neurons by releasing Ca²⁺ from IP₃ and ryanodine-sensitive intracellular stores and activating TRPC channels.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.90-90
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• 2017

Regulation of seed dormancy is important in many grains to prevent pre-harvest sprouting. To identify and understand the gene related to seed dormancy regulation, we have screened for viviparous phenotypes of rice mutant lines generated by insertion of Ds transposon in a Korean Japonica cultivar (Dongjin) background. One of the mutants, which represented viviparous phenotype, was selected for further seed dormancy regulation studies and designated dor1. The dor1 mutant has single Ds insertion in the second exon of OsDor1 gene encoding glycine-rich protein. The seeds of dor1 mutant showed a higher germination potential and reduced abscisic acid (ABA) sensitivity compared to wild type Dongjin. Over-expression of Dor1 complements the viviparous phenotype of dor1 mutant, indicating that Dor1 function in seed dormancy regulation. Subcellular localization assay of Dor1-GFP fusion protein revealed that the OsDor1 protein mainly localized to membrane and the localization of OsDOR1 was influenced by presence of a giberelin (GA) receptor OsGID1. Further bimolecular fluorescence complementation (BiFC) analysis indicated that OsDOR1 interact with OsGID1. The combined results suggested that OsDOR1 regulates seed dormancy by interacting with OsGID1 in GA response. Additionally, expression of OsDOR1 partially complemented the cold sensitivity of Escherichia coli BX04 mutant lacking four cold shock proteins, indicating that OsDOR1 possessed RNA chaperone activity.

• 생명과학회지
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• 제28권5호
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• pp.597-604
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• 2018

ADHD (Attention Deficit/Hyperactivity Disorder)은 4-17세의 아동 및 청소년의 약 10%가 겪는 흔한 신경 발달 장애이지만 그 핵심 기전이 알려져 있지 않은 가운데 관련한 여러 단백질들이 보고되어왔다. 이중 GIT1 (G-protein coupled-receptor kinase interacting protein-1)은 중추신경계에서 dendritic spine formation와 growth에 영향을 미치는 multifunctional adaptor protein으로, GIT1이 제거된 생쥐는 과잉행동, 주의력결핍 그리고 충동성을 보이는 ADHD 증상을 보이게 된다. 이 논문에서는 GIT1 유전자 변형 생쥐를 이용하여 genotype별로 신경교세포의 전달물질(gliotransmitter)을 비교 분석하는 실험을 진행하였다. 그 결과 주요 흥분성 전달물질인 glutamate는 HE (hetero)와 KO (knock-out)의 세포 내에서 WT (wildtype)보다 더 높은 농도로 존재했다. 한편, 억제성 신경전달물질인 GABA와 glycine의 경우 전반적으로 HE에서 가장 많은 함유량을 보였지만 소뇌 세포내의 경우, KO이 WT보다 많은 양을 함유한 것에 비해 대뇌 세포 내에서는 KO보다 WT의 억제성 전달물질 함유량이 높았다. 또한, glutamate와 GABA를 기준으로 흥분성/억제성 비율(excitation/inhibition ratio)을 보았을 때, 소뇌 세포 내/외 모두에서 KO이 가장 높은 수치를 보였고, 대뇌에서는 세포 내/외 모두 HE에서 가장 높은 수치를 보였다. 억제성 신경전달물질인 GABA가 KO의 대뇌 세포 외에서 가장 많은 것으로 보아 GIT1 결손을 보완하기 위해 억제성 물질을 더 많이 분비하거나 또는 과도하게 분비된 GABA를 재흡수하지 못하는 것이라 사료된다. 이는 ADHD 병리기전으로써 기능할 가능성을 제시하며 후속 연구를 통해 해당 기전에 대한 규명이 필요할 것으로 보인다.

• Asian-Australasian Journal of Animal Sciences
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• 제29권9호
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• pp.1256-1264
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• 2016

Adrenergic, alpha-1B-, receptor (ADRA1B) and peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B) genes are involved in regulation of hen ovarian development. In this study, these two genes were investigated as possible molecular markers associated with hen-housed egg production, egg weight (EW) and body weight in Chinese Dagu hens. Samples were analyzed using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, followed by sequencing analysis. Two novel single nucleotide polymorphisms (SNPs) were identified within the candidate genes. Among them, an A/G transition at base position 1915 in exon 2 of ADRA1B gene and a T/C mutation at base position 6146 in the 3'- untranslated region (UTR) of PPARGC1B gene were found to be polymorphic and named SNP A1915G and T6146C, respectively. The SNP A1915G (ADRA1B) leads to a non-synonymous substitution (aspartic acid 489-to-glycine). The 360 birds from the Dagu population were divided into genotypes AA and AG, allele A was found to be present at a higher frequency. Furthermore, the AG genotype correlated with significantly higher hen-housed egg production (HHEP) at 30, 43, 57, and 66 wks of age and with a higher EW at 30 and 43 wks (p<0.05). For the SNP T6146C (PPARGC1B), the hens were typed into TT and TC genotypes, with the T allele shown to be dominant. The TC genotype was also markedly correlated with higher HHEP at 57 and 66 wks of age and EW at 30 and 43 wks (p<0.05). Moreover, four haplotypes were reconstructed based on these two SNPs, with the AGTC haplotype found to be associated with the highest HHEP at 30 to 66 wks of age and with higher EW at 30 and 43 wks (p<0.05). Collectively, the two SNPs identified in this study might be used as potential genetic molecular markers favorable in the improvement of egg productivity in chicken breeding.