• BMB Reports
• /
• v.31 no.3
• /
• pp.264-268
• /
• 1998

Dopamine (DA) acts on swimming motor neurons (SMNs) of Polyorchis penicillatus as an inhibitory neurotransmitter by hyperpolarizing their membrane potentials, which results from the activation of voltagesensitive potassium channels mediated through a $D_2-type$ receptor. In addition, DA, and not the hyperpolarized membrane potential, directly decreased the input resistance of SMNs by ca. 50% from 1.42 to 0.68 $G{\Omega}$. It strongly indicates that DA can shunt other excitatory synaptic signals onto SMNs where DA usually elicited much greater responses in their neurites than soma. All these evidences suggest that DA may operate in this primitive nervous system in dual modes as an inhibitory neurotransmitter and neuromodulator as well.

• Toxicological Research
• /
• v.14 no.3
• /
• pp.349-356
• /
• 1998

We identified S9940, a novel microbial metabolite from Streptomyces spp., to inhibit the release of neurotransmitter from PC12 cells. S9940 is an inhibitor of trifiated norepinephrine ([$^{3}H$]-NE) release in high $K^+$ buffer solution containing ionomycin, indicating that S9940 inhibits neurotransmitter release after the influx of $Ca^{2+}$ ions. We also examined the effect of S9940 on $\beta-glucuronidase$ release from guinea pig neurophils and the effect on the neurite extension of PC12 cells and rat hippocampal neurons. As a result, S9940 inhibited $\beta-glucuronidase$ release: when treated with $5{\mu}g/ml$ of S9940, which prevented [$^{3}H$]-NE release, the inhibition of neurite extension for both PC12 cells and rat hippocampal neurons was observed.

• Korean Journal of Microbiology
• /
• v.31 no.3
• /
• pp.224-229
• /
• 1993

GABA transminase (4-aminobutyrate aminotransferase), which catalyzes the breakdown of the major inhibitory neurotransmitter, GABA, in mammalian brain, was inactivated by preincubation with the mycotoxin patulin. The time course of the reaction was significantly affected by the substrate .alpha.-ketoglutarate, which aforded complete protection against the loss of catalytic activity. The recovery from the inhibition of patulin by the addition of dithiothreitol (DTT) supports that patulin reacts with the sulfhydryl residue in the catalytic domain of the enzyme. The reconstitution of the reduced enzyme and apoenzyme with pyridoxal-5-P(PLP) was inhibited by another mycotoxin, penicilic acid. This mycotoxin may interact with lysyl residue of the enzyme. Therefore, it is postulated that the critical sulfhydryl and lysyl residues in the catalytic domain of the enzyme react with mycotoxin patulin and penicillic acid, respectively.

• Anxiety and mood
• /
• v.2 no.2
• /
• pp.79-85
• /
• 2006

Anxiety and anxiety disorders are related to many neurotransmitters, such as norepinephrine, serotonine, dopamine, glutamate, and Gamma-aminobutyric acid (GABA). GABA, the main inhibitory neurotransmitter of the CNS, is known to counterbalance the action of the excitatory neurotransmitters and control anxiety. GABA acts on 3 GABA receptor subtypes, $GABA_A$, $GABA_B$, and $GABA_C$. $GABA_A$ and $GABA_c$ receptors are oligomeric transmembrane glycoproteins composed of 5 subunits that are arranged around a central chloride channel. $GABA_B$ receptor comprises two 7-transmembraneis-spanning proteins that are coupled to either calcium or potassium channel via G proteins. This article highlights neurobiological interactions between anxiety and GABA system.

• The Zoological Society Korea : Newsletter
• /
• v.18 no.2
• /
• pp.12-20
• /
• 2001

2000년도 노벨 의학상은 스웨덴의 아비스 칼슨 박사 등 3명 이 수상했다. 그들은 신경전달 물질(neurotransmitter) 중 도파민 (dopamine)과 시냅스(synapse)에 관한 연구로 항 우울제 치료제인 프로작 (prozac)을 개발하여 신경, 정신질환 치료제 개발에 기여한 공로였다. 도파민과 GABA는 신경전달 물질 중의 하나로 도파민은 운동, 정서, 행동, 희노애락 등을 조절하는 것으로 이상 분비될 때 파킨스씨병, 정신분열증, 우울증 등을 유발시킨다. GABA는 억제성 신경전달물질로 이상 분비시 간질 등을 유발시킨다. 도파민과 GABA의 분비는 시냅스 후(postsynapse) 수용체에서 그 기능이 조절된다. 그러나 마약성인 코카인, 헤로인, 몰핀, 암페타민 등 중 독성약물뿐만 아니라 일상 생활에서 흔히 접할 수 있는 흡연, 술 등에 의해서도 그 분비 이상을 초래한다. 따라서 본 논단에서는 최근 뇌신경생물 실험실에서 진행되고 있는 신경전달 물질 중에 도파민 및 GABA 분비에 대 한 연구결과를 바탕으로 소개 하고자 한다.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• v.16 no.1
• /
• pp.15-25
• /
• 2005

During the recent decade, the new data about normal neurochemical system development have been accumulated very much. Based on these new data, the up-to-date theory and hypothesis have been developed. These development of this field results from the technological/methodological development which increase the sensitivity, specificity and validity of neurochemical research. Especially, molecular technological development support the recent neurochemical development. In this review article, the authors described the recent research findings in the field of normal neurochemical development of neurotransmitter system in animal and human. Most of child psychiatric disorder, especially neuropsychiatric developmental disorders (ADHD, Autism, Tourette's disorder, MR etc) seem to have underlying neurochemical developmental problems in the pathophysiological basis. So, the data on the normal ontogeny of neurotransmitter system can be the most valuable resources for the research on the etiology of the diverse child psychiatric disorders.

• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.6
• /
• pp.295-301
• /
• 2003

Striatum plays a crucial role in the movement control and habitual learning. It receives an information from wide area of cerebral cortex as well as an extensive serotonergic (5-hydroxytryptamine, 5-HT) input from raphe nuclei. In the present study, the effects of 5-HT to modulate synaptic transmission were studied in the rat corticostriatal brain slice using in vitro extracellular recording technique. Synaptic responses were evoked by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. 5-HT reversibly inhibited coticostriatal glutamatergic synaptic transmission in a dose-dependent fashion (5, 10, 50, and $10{\mu}M$), maximally reducing in the corticostriatal population spike (PS) amplitude to $40.1{\pm}5.0$% at a concentration of $50{\mu}M$ 5-HT. PSs mediated by non-NMDA glutamate receptors, which were isolated by bath application of the NMDA receptor antagonist, d,l-2-amino-5-phospohonovaleric acid (AP-V), were decreased by application of $50{\mu}M$ 5-HT. However, PSs mediated by NMDA receptors, that were activated by application of zero $Mg^{2+}$ aCSF, were not significantly affected by $50{\mu}M$ 5-HT. To test whether the corticostriatal synaptic inhibitions by 5-HT might involve a change in the probability of neurotransmitter release from presynaptic nerve terminals, we measured the paired-pulse ratio (PPR) evoked by 2 identical pulses (50 ms interpulse interval), and found that PPR was increased ($33.4{\pm}5.2$%) by 5-HT, reflecting decreased neurotransmitter releasing probability. These results suggest that 5-HT may decrease neurotransmitter release probability of glutamatergic corticostriatal synapse and may be able to selectively decrease non-NMDA glutamate receptor-mediated synaptic transmission.

• Journal of Life Science
• /
• v.6 no.2
• /
• pp.142-148
• /
• 1996

Aloe(Aloe arborescens M$_{ILL}$) has been used as a home medicine for the past several thousand in the world, and has been studied on anti-bacterial and anti-fungal activities, hypotension, atherosclerosis, myocardiac infartion, apoplexy, diabetes as a chronic digenerative disease, tumors, gastrointestinal tract, liver and pancreas' diseases, and genitourinary tract etc. SAMP8 as a learing and memory impairment animal model were fed basic and/or experimental diets with 1.0% freezing dried(FD)-aloe for 8 months. The passive avoidance tests such as acqusition trial and retention test were significantly higher in aloe group than in control group. Grading score of senescence resulted in a marked decreases in aloe group compared with control group. Acetylcholinesterase(AChE) activity was remarkably increased in aloe group compared with control group. Neurotransmitters such as dopamine(DA) and serotonin(5-HT) almost did not change by the feeding of aloe-added diet, but their metabolites such as homovanillic acid(HVA) and 5-hydroxy-indole acetic acid(5-HIAA) in aloe group were significantly increased compared with control group. Therefore, the ratios of HVA/DA and 5-HIAA/5-HT as a ratio of metabolite on neurotransmitter were significantly increased by the feeding of aloe-added diet. These results suggest that aloe vara may be activated acetylcholinesterase, the metabolite of neurotransmitter, and ratios of metabolite on neurotransmitter, resulting ina greater prevention of learning and memory impairments such as Alzheimertype dementia.

• Biomolecules & Therapeutics
• /
• v.30 no.2
• /
• pp.191-202
• /
• 2022

Tetrazoles were designed and synthesized as potential inhibitors of triple monoamine neurotransmitters (dopamine, norepinephrine, serotonin) reuptake based on the functional and docking simulation of compound 6 which were performed in a previous study. The compound structure consisted of a tetrazole-linker (n)-piperidine/piperazine-spacer (m)-phenyl ring, with tetrazole attached to two phenyl rings (R1 and R2). Altering the carbon number in the linker (n) from 3 to 4 and in the spacer (m) from 0 to 1 increased the potency of serotonin reuptake inhibition. Depending on the nature of piperidine/piperazine, the substituents at R1 and R2 exerted various effects in determining their inhibitory effects on monoamine reuptake. Docking study showed that the selectivity of tetrazole for different transporters was determined based on multiple interactions with various residues on transporters, including hydrophobic residues on transmembrane domains 1, 3, 6, and 8. Co-expression of dopamine transporter, which lowers dopamine concentration in the biophase by uptaking dopamine into the cells, inhibited the dopamine-induced endoctytosis of dopamine D₂ receptor. When tested for compound 40 and 56, compound 40 which has more potent inhibitory activity on dopamine reuptake more strongly disinhibited the inhibitory activity of dopamine transporter on the endocytosis of dopamine D₂ receptor. Overall, we identified candidate inhibitors of triple monoamine neurotransmitter reuptake and provided a theoretical background for identifying such neurotransmitter modifiers for developing novel therapeutic agents of various neuropsychiatric disorders.

• Korean Journal of Biological Psychiatry
• /
• v.2 no.1
• /
• pp.3-19
• /
• 1995

Numerous investigators have conducted extensive investigation in the search for biological markers in psychiatric illness. There are, as a test of q biological approach to the diagnosis of the psychiatric illness, tests for the neurotransmitters, their metabolites, and related enzymes, the neurotransmitter receptors, the neuroendocrine output and response, the membrane transport, peptides and eletrolytes. They are called the biological markers, and they are helpful for the diagnosis or differential diagnosis, choice of treatment or drugs, symptom improvement, predictor of recurrence and anticipation of suicidal attempt. These studies are among the main purposes that are pursued in the neuroscience and based on the potential utility of the biological markers mentioned above. Since 1970's, lots 01 biological markers' studies for the diagnosis, differential diagnosis or subtypes differentiation have been done but varieties of different opinions have been drawn since then through they could explain the charaters of main psychiatric illness(especially schizophrenia and mood disorder). But, the search for biological markers, including displines of neuroendoclinology and neurochemistry(neurotransmitter and thair metabolite), has yielded a number of putative trait merkers and state markers for psychayric illness. This paper aims to anticipate or evaluate the good response to the therapy(Therpeutic response) with lots of markers. Acoording to the diagnosis of lots of diseases or subtypes, we are going to review the papers, mainly concern with 'Is there any Marker' or 'Is any test possible to detect the improvement clinically?' 'Is it possible to predict the recurrence or good prognsis?' or 'Is it possible to select any drug or therapy to bring the good response?' The biological tests to review are mainly the metabolites of catecholamine neurotransmitter, and especially neuroendocrine test based on the knowledge that hormons of the adenohypophysis are influenced by activity of the cerebral or limbic neurons as well as the hypothalamus ones. Among them, author introduced some clinically available tests that are DST, TRH stimulation test(TRHST), GH stimulation test, and the urine MHPG test that can give us the evaluation of the treatment response, the predictor for recurrence or choice of drug that can bring a good response. So author discussed thair potential utility in clarifying, therapeutic, and prognostic issues in psychatric illness. We hope they'll be used and look forward to more active study on the different opinion.