• Biomolecules & Therapeutics
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• v.20 no.1
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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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• v.15 no.2
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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.

• Journal of Life Science
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• v.5 no.1
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• pp.33-44
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• 1995

• Biomedical Science Letters
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• v.6 no.3
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• pp.165-170
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• 2000

Vacuolar (H$^{+}$)-ATPase (V-ATPase) is an intracellular protein which consists of multiple subunits. It carries out acidification by pumping protons in the cell. This enzyme has also been found in the synaptic vesicles and may play an important role in the neurotransmission. We cloned cDNA fragments encoding the 16 kDa subunit of V-ATPase from the rat brain by RT-PCR and PCR using total RNA or recombinant phage DNA as templates. They contained the full coding sequences (468 bp) and one nucleotide at 3' region turned out to be different (A to C) when compared to the liver counterpart. However, this polymorphic difference did not cause any significant change in the primary structure of the protein because both GCA and GCC code for alanine. Our study would contribute to the understanding of the function of 16 M)a V-ATPase in the brain and of the mechanisms of neurotransmission.

• YAKHAK HOEJI
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• v.44 no.1
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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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• v.43 no.9
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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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• v.20 no.2
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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.

• The Korean Journal of Nuclear Medicine
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• v.31 no.4
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• pp.401-420
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• 1997

• Archives of Pharmacal Research
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• v.18 no.2
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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.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.75-86
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• 1994

To assess the role of adrenal medulla and renin-angiotensin system in the regulation of sympathetic neurotransmission, the pressor response to PNS was evaluated in pithed SHR and normotensive WKY or SDR with or without adrenal demedullation and/or enalapril pretreatment. Three weeks after adrenal demedullation, MAP and the heart rate of demedullated rats were similar to their corresponding sham-operated groups. The pressor response to PNS was frequency-dependent, and blocked by prazosin. In contrast to the normotensive rats, in SHR, the pressor response to PNS was attenuated in demedullated rats as compared with sham-operated rats. However, the attenuation of PNS-induced pressor responses in demedullated SHR was not observed in enalapril-treated SHR. The adrenal demedullation in SHR did not affect the plasma and aortic catecholamine contents in spite of the decreased catecholamine contents of adrenal gland, nor ACE activity in aortic strips. But, in WKY rats, the aortic catecholamines, especially epinephrine, contents as well as ACE activity were increased by adrenal demedullation. These results suggest that the facilitatory role of adrenal medulla in sympathetic neurotransmission depends upon the activation of renin-angiotensin system, and that the compensatory regulation of renin-angiotensin system takes place in normotensive rats but not in SHR.