• Biomolecules & Therapeutics
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• 제20권1호
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• pp.1-18
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• 2012

Schizophrenia is a devastating psychiatric illness that afflicts 1% of the population worldwide, resulting in substantial impact to patients, their families, and health care delivery systems. For many years, schizophrenia has been felt to be associated with dysregulated dopaminergic neurotransmission as a key feature of the pathophysiology of the illness. Although numerous studies point to dopaminergic abnormalities in schizophrenia, dopamine dysfunction cannot completely account for all of the symptoms seen in schizophrenia, and dopamine-based treatments are often inadequate and can be associated with serious side effects. More recently, converging lines of evidence have suggested that there are abnormalities of glutamate transmission in schizophrenia. Glutamatergic neurotransmission involves numerous molecules that facilitate glutamate release, receptor activation, glutamate reuptake, and other synaptic activities. Evidence for glutamatergic abnormalities in schizophrenia primarily has implicated the NMDA and AMPA subtypes of the glutamate receptor. The expression of these receptors and other molecules associated with glutamate neurotransmission has been systematically studied in the brain in schizophrenia. These studies have generally revealed region- and molecule-specifi c changes in glutamate receptor transcript and protein expression in this illness. Given that glutamatergic neurotransmission has been implicated in the pathophysiology of schizophrenia, recent drug development efforts have targeted the glutamate system. Much effort to date has focused on modulation of the NMDA receptor, although more recently other glutamate receptors and transporters have been the targets of drug development. These efforts have been promising thus far, and ongoing efforts to develop additional drugs that modulate glutamatergic neurotransmission are underway that may hold the potential for novel classes of more effective treatments for this serious psychiatric illness.

• Archives of Pharmacal Research
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• 제15권2호
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• pp.134-137
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• 1992

The effect of papaverine on the contractions induced by adrenergic neurotransmission in the isolated mouse vas deferens was investigated. Papaverine, $10^{-7}-10^{-5}$M, showed a dose-dependent and reversible inhibition on the induced contractions. When the frequency of stimulation was varied (2.5-20.0 Hz), the inhibitory effect tended to be marked at the lower frequencies.

• 생명과학회지
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• 제5권1호
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• pp.33-44
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• 1995

• 대한의생명과학회지
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• 제6권3호
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• pp.165-170
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• 2000

Vacuolar (H$^{+}$)-ATPase (V-ATPase)는 multi-subunit로 구성된 단백질로서, proton pumping을 통해 세포내 산성화반응에 관여를 한다. 최근에 이 단백질이 synaptic vesicle에서도 발견된 것으로 보아 뇌 신경전달에 중요한 역할을 수행할 것으로 추정하고 있다. 우리는 흰쥐 뇌에서 분리한 mRNA를 주형으로 한 PCR 반응에서 16 kDa subunit의 V-ATPase cDHA를 클로닝할 수 있었고, 이의 염기서열 또한 결정하였다. 분리된 뇌 16 kDa V-ATPase의 coding sequence는 전체 468 bp로서 간에서 보고되었던 것과 동일한 크기였다. 단지 3' 말단의 염기 하나가 A에서 C로 바뀌어 있었는데 모두 alanine (GCA, GCC)을 지정하기 때문에 단백질의 일차구조에는 변화가 없는 것으로 확인되었다. 한편 rat brain cDNA library에서도 동일한 clone이 분리되었는데 역시 같은 부분에서 polymorphism이 발견되었고, RNA splicing 등 더 이상의 조직특이적 변화는 없었다. 본 연구는 16 kDa V-ATPase의 뇌에서의 기능과 신경말단에서의 neurotransmission 및 synaptic vesicle의 재순환 기전을 이해하는데 유용한 정보가 될 것이다.

• 약학회지
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• 제44권1호
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• pp.22-28
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• 2000

The extracts of Euphoria longan, Ziryphus jujuba, Thuja orientalis, Polygala tenuifolia, Acorus gramineus, Cyperus rotundus, Poria cocos, Uncaria rhynchophylla, and Albizzia julibrissin, which have been used as sedative drugs in Korean folk medicine, were evaluated for their effects on neurotransmission and antioxidative system in vitro. Among the tested drugs, Acorus gramineus showed most inhibitory activities on monoamine oxidase, xanthine oxidase, aldehyde oxidase, and lipid peroxidation and Uncaria rhynchophylla also inhibited most effectively GABA transaminase and DPPH radical.

• BMB Reports
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• 제43권9호
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• pp.593-598
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• 2010

Tetrahydrobiopterin ($BH_4$) is a pivotal cofactor for enzymes responsible for the synthesis and release of monoamine neurotransmitters including dopamine and serotonin as well as the release of glutamate. Deficiencies in $BH_4$ levels and reduced activities of $BH_4$-associated enzymes have been recently reported in patients with schizophrenia. Accordingly, it is possible that abnormalities in the biochemical cascades regulated by $BH_4$ may alter DA, 5-HT and Glu neurotransmission, and consequently contribute to the pathophysiology of different neuropsychiatric diseases including schizophrenia. The development of a novel strain of mutant mice that is deficient in $BH_4$ by knocking out the expression of a functional sepiapterin reductase gene (spr -/-) has added new insights into the potential role of $BH_4$ in the pathophysiology and improved treatment of schizophrenia.

• Biomolecules & Therapeutics
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• 제20권2호
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• pp.152-157
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• 2012

Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the brain and a structural component of neuronal membranes. Changes in DHA content of neuronal membranes lead to functional changes in the activity of receptors and other proteins which might be associated with synaptic function. Accumulating evidence suggests the beneficial effects of dietary DHA supplementation on neurotransmission. This article reviews the beneficial effects of DHA on the brain; uptake, incorporation and release of DHA at synapses, effects of DHA on synapses, effects of DHA on neurotransmitters, DHA metabolites, and changes in DHA with age. Further studies to better understand the metabolome of DHA could result in more effective use of this molecule for treatment of neurodegenerative or neuropsychiatric diseases.

• 대한핵의학회지
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• 제31권4호
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• pp.401-420
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• 1997

• Archives of Pharmacal Research
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• 제18권2호
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• pp.121-128
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• 1995

The role of nitric oxide (NO) in non-adrenegic non-cholinergic (NANC) neurotransmission was studied on circular muscle strips of the dorsal part of the fuinea-pig gastric fundus. In the presence of atropine and guanethidine, a low frequency-dependent relaxsations which were not affected by adrenergic and cholinergic blockage but abolished by tetrodotoxin. $N^G$-nitro-L-arginine (L-NNA), a stereospecific inhibitor of NO-biosynthesis, inhibited the relaxations induced by electrical stiumulations but not the relaxations to exogenous nitric oxide. The effect of L-NNA was prevented by L-arginine, the precursor of the NO biosynthesis but not by its enantiomer, D-arginine. Exgenous administration of No caused concentration -dependent relaxations which showed a similarity to those obtained with electrical simultaion. Hemoglobin, a NOscavenger, abolished the NO-induced relaxations and also markedly reduced those induced by electrical simultaion. The inhibitory effect os hemoglobin was similar to that of L-NNA. Application of ATP caused weak relaxations compared with those to electrical stimultaion, which were unaffected by L-NNA. Exogenously applied vasoactive intestinal polypeptide (VIP) induced concentration-dependent relaxation which was not affected by L-NNA. These results suggest that NO is produced and released mainly as a neurotransmitter from enteric neurons during NANC relaxation induced by low frequencies and short trains of electrical simulation and has a main role in NANC neurotransmission at relaxation induced by these electrical simultaions in the guinea-pig gastric fundus.

• 대한약리학회지
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• 제30권1호
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• pp.75-86
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• 1994

선천성 고혈압 흰쥐(SHR)와 정상혈압 흰쥐에서 교감신경성 신경전달에 미치는 부신수질 및 renin-angiotensin계의 역할을 알아보기 위해, 부신수질을 제거하거나 angiotensin 변환 효소 억제제를 장기간 처치한 뒤 중추신경계가 파괴된 상태에서 절전신경을 자극했을 때 나타나는 승압반응과 대동맥의 catecholamine농도 및 angiotensin 변환 효소 활성도의 변화를 비교 검토하였다. 부신수질을 제거하더라도 중추신경계를 파괴하기 전후의 혈압에는 영향을 주지 못했으며, 절전 신경 자극에 의한 승압반응은, 자극 주파수에 의존적으로 증가하였으며 prazosin 전처치로서 거의 완전히 억제되었다. 정상혈압 흰쥐에서와는 달리, 선천성 고혈압 흰쥐에서는 부신수질을 제거했을 때는 절전신경 자극에 의한 승압반응이 부신수질을 제거하지 않는 군(이하 대조군)에 비하여 유의하게 약화되었다. SHR에서 부신수질 제거로 부신 catecholamine 함량은 현저히 감소되었고, 혈청의 angiotensin 변환 효소 활성도는 감소되는 경향을 나타내었다. 그러나 혈장 및 대동맥 절편의 catecholamine 함량, 대동맥 절편의 angiotensin 변환 효소의 활성도는 대조군과 유의한 차이가 없었다. 그러나 WKY에서는 부신수질이 제거된 군에서 대동맥 절편의 angiotensin 변환 효소의 활성도와 catecholamine함량이 대조군에 비해 유의하게 증가되어 있었다. Enalapril처치에 의해서 선천성 고혈압 흰쥐 평균 혈압은, 부신 catecholamine 함량 및 대동맥 절편의 angiotensin 변화 효소의 활성도와 함께 현저히 저하되어 정상혈압 흰쥐와 유사하였다. 그리고 선천성 고혈압 흰쥐에서 부신수질의 제거로 절전신경 자극에 의한 승압반응이 대조군에 비하여 약화되는 현상은 enalapril을 처치하였을 때는 관찰되지 않았다. 이상의 결과로 미루어보아 교감신경성 신경전달을 항진시키는 부신수질의 작용은 renin-angiotensin계의 활성화에 의존적이었으며, 부신수질의 제거로 정상혈압 흰쥐에서는 renin-angiotensin계가 보상적인 조절이 일어났으나, 선천성 고혈압 흰쥐에서는 보상적인 조절이 일어나지 않았다.