• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.699-705
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• 1997

Although it is known that neuronal cell death during development occurs by apoptosis, the mechanisms underlying excitatory amino acid-induced neuronal cell death remain poorly understood. In this study we have examined the mechanism by which L-glutamate, an excitatory amino acid neurotransmitter, induces cell death in PC12 cell lines. To characterize cell death, we employed sandwich enzyme-linked immunosorbent assay(ELISA) method for cellular DNA fragmentation, DNA agarose gel electrophoresis and chromatin staining by acridine orange and ethidium bromide after treating the PC12 cells with L-glutamate. L-Glutamate caused dose-dependent cell death with a maximum at 24 hrs after the treatment. These cellular fragmentation was blocked by pretreatment of MK-801, a noncompetitive N-methyl-D-aspartic acid(NMDA) receptor antagonist, and nerve growth factor(NGF). Analysis of DNA integrity from L-glutamate-treated cells revealed cleavage of DNA into regular sized fragments, a biochemical hallmark of apoptosis. The PC12 cells that were induced to die by L-glutamate treatment exhibited classical chromatin condensation under the light microscopy after acridine orange and ethidium bromide staining. These results suggest that apoptosis is one of the key features that are involved in L-glutamate-induced excitotoxic cell death in PC12 cells, and these cell death are mediated by NMDA receptor and depend on NGF.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.2
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• pp.189-197
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• 2001

To investigate propofol's effects on ionic currents induced by ${\gamma}-aminobutyric$ acid (GABA) and glycine as well as on those produced by the nicotinic acetylcholine- and glutamate-responsive channels, rat dorsal raphe neurons were acutely dissociated and the nystatin-perforated patch-clamp technique under voltage-clamp conditions was used to observe their responses to the administration of propofol. Propofol evoked ion currents in a dose-dependent manner, and propofol $(10^{-4}\;M)$ was used to elicit ion currents through the activation of $GABA_A,$ glycine, nicotinic acetylcholine and glutamate receptors. Propofol at a clinically relevant concentration $(10^{-5}\;M)$ potentiated $GABA_A-,$ glycine- and NMDA receptor-mediated currents. The potentiating action of propofol on $GABA_A-,$ glycine- and NMDA receptor-mediated responses involved neither opioid receptors nor G-proteins. Apparently, propofol modulates inhibitory and excitatory neurotransmitter-activated ion channels either by acting directly on the receptors or by potentiating the effects of the neurotransmitters, and this modulation appears to be responsible for the majority of the anaesthetic and/or adverse effects.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.3
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• pp.151-156
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• 2010

This study was performed to investigate the role of glutamate neurotransmitter system on gastrointestinal motility in a middle cerebral artery occlusion (MCAO) model of rats. The right middle cerebral artery was occluded by surgical operation, and intestinal transit and geometric center as a parameter of gastrointestinal motility and expression of c-Fos protein in the insular cortex and cingulate cortex were measured at 2 and 12 h after MCAO. Intestinal transit was $66.3{\pm}7.5%$ and $62.3{\pm}5.7%$ 2 and 12 h after sham operation, respectively, and MCAO significantly decreased intestinal transit to $39.0{\pm}3.5%$ and $47.0{\pm}5.1%$ at 2 and 12 h after the occlusion, respectively (p<0.01). The geometric center was $5.6{\pm}0.4$ and $5.2{\pm}0.9$ at 2 and 12 h after sham operation, respectively, and MCAO significantly decreased geometric center to $2.9{\pm}0.8$ and $3.0{\pm}0.3$ at 2 and 12 h after the occlusion, respectively (p<0.01). In control animals, injection of atropine decreased intestinal transit to $35.9{\pm}5.2%$, and injection of glutamate NMDA receptor antagonist, MK-801, decreased intestinal transit to $28.8{\pm}9.5%$. Pretreatment with MK-801, a glutamate NMDA receptor antagonist, in the MCAO group decreased intestinal transit to $11.8{\pm}3.2%$, which was significantly decreased compared to MCAO group (p<0.01). MCAO markedly increased the expression of c-Fos protein in the insular cortex and cingulate cortex ipsilateral to the occlusion 2 h after MCAO, and pretreatment with MK-801 produced marked reduction of c-Fos protein expression compared to MCAO group (p<0.01). These results suggest that modulation of gastrointestinal motility after MCAO might be partially mediated through a glutamate NMDA receptor system.

• Journal of Yeungnam Medical Science
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• v.12 no.2
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• pp.246-259
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• 1995

This study aimed to investigate the mechanism of action of baclofen on the detrusor muscle isolated from rat. Rats (Sprague-Dawley) were sacrificed by decapitation and exsanguination. Horizontal muscle strips of $2mm{\times}15mm$ were prepared for isometric myography in isolated muscle chamber bubbled with 95% / 5%-$O_2$ / $CO_2$ at $37^{\circ}C$, and the pH was maintained at 7.4. Detrusor strips contracted responding to the electrical field stimulation (EFS) by 2 Hz, 20 msec, monophasic square wave of 60 VDC. The initial peak of EFS-Induced contraction was tended to be suppresed by ${\alpha},{\beta}$-methylene-adenosine 5'-triphosphate (mATP), a partial agonist of purinergic receptor, and baclofen, a $GABA_B$ receptor agonist (statistically nonsignificant). The late sustained contraction by EFS was suppressed significantly (p < 0.05) by additions of atropione, a cholinergic muscarinic receptor antagonist and baclofen. The adenosine 5'-triphosphate-induced contraction was completely abolished by mA TP but not by baclofen. In the presence of atropine, the subsequent addition of acetylcholine could not contract the muscle strips: but the addition of acetylcholine in the presence of baclofen evoked a contraction to a remarkable extent. These results suggest that in the condition of present study, the cholinergic innervation may play a more important role than the purinergic one, and baclofen suppresses the contractility of rat detrusor by the stimulation of the $GABA_B$ receptors to inhibit the release of neurotransmitter from the cholinergic nerve ending.

• YAKHAK HOEJI
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• v.44 no.1
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• pp.52-59
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• 2000

An exceptionally conserved sequence that is shared among most G protein-coupled neurotransmitter receptors is an aspartate-arginine-tyrosine triplet that is located at the second cytoplasmic domain. Using the ml subtype of muscarinic acetylcholine receptors as an example, a point mutation of the arginine residue at position 123 into asparagine was induced. This mutation resulted in a complete blockade of the carbachol-induced increases of PI hydrolysis and intracellular $Ca^2$$^{+}$ level, in spite of the expression of the wild-type and mutant receptors at similar concentrations in Chinese hamster ovary cells. In marked contrast, the muscarinic agonist carbachol induced concentration-dependent enhancement of the activity of NO synthase at mutant ml receptors although the enhancement was significantly smaller than at wild-type ml receptors. These data suggest that this highly conserved arginine residue plays an important role in coupling of muscarinic receptors to the second messenger systems and the presence of alternate mechanisms of activation of neuronal NO synthase which might be operative in the absence of large changes in the concentration of cellular $Ca^{2+}$.2+/.

• Journal of Biomedical Engineering Research
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• v.30 no.1
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• pp.89-93
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• 2009

Bone remodeling is a continuous process of skeletal renewal during which bone formation is tightly coupled to bone resorption. Mechanical loading is an important regulator of bone formation and resorption. In recent studies, neurotransmitters such as vasoactive intestinal peptide (VIP) were found to be present inside bone tissue and have been suggested to potentially regulate bone remodeling. In this study, our objective was to use a pre-established in vitro oscillatory fluid flow-induced shear stress mechanical loading system to quantify the effect of VIP on bone resorptive activity and investigate its combined effect with mechanical loading. VIP decreased osteoclastogenesis significantly decreased RANKL/OPG mRNA ration by approximately 90%. Combined VIP and mechanical loading further decreased RANKL/OPG ratio to approximately 95%. These results suggest that VIP present in bone tissue may synergistically act with mechanical loading to regulate bone remodeling via suppression of bone resorptive activities.

• Korean Journal of Biological Psychiatry
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• v.12 no.1
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• pp.3-12
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• 2005

Most suicides(about 90%) occur in the context of psychiatric disorders. Prediction of suicide risk in patients with mental illness is very important in preventing suicide attempts. However, current approaches to predict suicidality are based on clinical history and have low specificity and biological markers are not yet included. Many studies have explored the association between different biological parameters and suicidality. Studies of cerebro-spinal fluid(CSF) demonstrated that 5-HIAA and HVA levels were lower in patients with a history of suicide. Platelet serotonin transporter and the 5-HT2 serotonin receptor have also been studied in relation to violence and suicide. Depressive patients with greater suicidal tendency had significantly lower cholesterol concentrations but some researchers failed to find the correlation. DST non-supression is reported to predict suicidality in major depression. Several studies demonstrated a relationship between intron 7 polymorphism of tryptophan hydroxylase and suicidal behavior. Since suicide is not occurred in a single disease, the systematic and comprehensive study in large samples with various diagnoses is necessary to find the biological and genetic predictors of suicidal behavior.

• Journal of Oriental Neuropsychiatry
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• v.24 no.3
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• pp.257-262
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• 2013

Objectives : Aripiprazole is unique drug among the SGA (Second generation antipsychotics) in its pharmacology and pharmacokinetics,but is similar in clinical efficacy. Aripiprazole acts as a partial agonist at dopamine D2 receptors, activating the receptor but eliciting a reduced response compared to the natural neurotransmitter. There are some side effects of aripiprazole, the most common side effects of aripiprazole are headache, nausea, vomiting, insomnia, tremor, constipation and EPS. Difficulty in opening eyes is not defined EPS yet, but it is a rare but important side-effect symptom of aripiprazole. Methods : This article is about a case of side-effect symptom of aripiprazole, 26-year-old single female suffering from schizophrenia had difficulty in opening eyes while she was taking antipsychotics. During the hospitalization, the relaxation therapy is helpful not only to reduce tension in the eyelids but also to headache. Results : It is important that early recognition of aripiprazole-induced oculogyric dystonia can prevent life-threatening complications. Education medical staff to this easily treatable reaction will improve overall quality of health care. Conclusions : This case notifies the need for awareness of the risk of acute oculogyric dystonia in adolescent female patients receiving aripiprazole.

• The Korean Journal of Zoology
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• v.29 no.4
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• pp.235-244
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• 1986

In order to elucidate the effect of neurotransmitter on the differention of myoblasts in vitro, dopamine was administered to the myoblasts at varying stages of myogenesis, and the fusion index, the rate of creatine kinase (CK) synthesis, and the sensitivity to dopamine were determined. When dopamine $(3 \\times 10^{-5} M)$ was administered at 34 hr after myoblast seeding, a significant decrease in the fusion index as well as CK synthesis was observed, indicating a good correlation exists between these two parameters. In other experiment, dopamine was administered at varying stages of myogenesis and the inhibitory effect of dopamine as scored by fusion index at 96 hr was found to be cyclic in nature. This finding raised a possibility that arrangement of dopamine receptors occurs according to the cell cycle stages in myogenesis.

• Journal of Acupuncture Research
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• v.20 no.6
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• pp.89-102
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• 2003

Objective: The expression of CRF(corticotropin releasing factor), CRF-R(receptor) and CRF-BP(binding protein) in CNS neurons projecting to the stomach and ST36 using the pseudorabies virus in the rat was investigated. Methods: After survival times of 5 days following injection of PRV-Ba-Gal, The thirty rats were perfused, and their brain were frozen sectioned($30{\mu}m$). These sections were stained by PRV-Ba-Gal histochemical staining method and(or) CRF, CRF-R and CRF-BP immunohistochemical method. The common expressed areas of the brain projecting to the stomach and zusanli(ST36) following injection of PRV-Ba-Gal were observed with light microscope. Results: 1) The dense accumulation of CRF-immunoreactive terminals is seen in the area postrema, n. tractus solitarius, external zone of the median eminence, with some immunoreactive CRF also present in the internal zone. 2) Aggregates of CRF-R immunoreactive perikarya are found in area postrema, n. tractus solitarius, lateral reticular n., gigantocellular reticular n., locus coeruleues, paraventricular n. of hypothalamus, median eminence, preoptic n., arcuate n. and hind limb area of cerebral cortex. 3) Aggregates of CRF-BP immunoreactive perikarya are found in area postrema, n. tractus solitarius, lateral reticular nucleus, gigantocellular reticular n., locus coeruleues, paraventricular n. of hypothalamus, median eminence and arcuate n.. Conclusions : These results suggest that PRV-Ba-Gal labeled areas projecting to stomach and ST36 may be related to the central autonomic pathways. A part of CNS neurons projecting to the stomach and ST36 were related to expression of CRF, CRF-R and CRF-BP related to the stress in central autonomic center.