• Journal of Life Science
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• v.22 no.8
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• pp.1046-1051
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• 2012

In order to investigate the changes in bioactive materials induced in goldfish brains by $^{18}F$ irradiation, the variations in the neurotransmitter levels in the whole brain were studied. The distance between the goldfish and 580 mCi of $^{18}F$ was about 4 cm, and the exposure lasted for 4 hrs. The absorption level calculated based on the distance, exposure time, and half-life of $^{18}F$ was approximately 2 Gy. After sacrifice by $^{18}F$ irradiation or untreated conditions, ten brains were dissected or immediately frozen, respectively. The tissues were extracted in acetic acid. After lyophilization, the samples were dissolved in distilled water and were further purified on a reverse-phase HPLC column. There were no differences in the intensities of the bioactive materials between $^{18}F$-exposed goldfish and control goldfish, while the only peak corresponded to 13 min, which indicated a significant increase in the irradiated brains. Our analysis has found that this compound is tryptophan. This result suggests that $^{18}F$ leads to changes in a classical neurotransmitter, tryptophan, in both the brains of control goldfish and goldfish contaminated by irradiation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.982-992
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• 2005

Acupuncture as a therapeutic intervention is widely used for the treatment of many functional disorders such as substance abuse and mental dysfunction. Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug addiction. Yet, there are still many unanswered questions about the basic mechanism of acupuncture. Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and raised the possibility that both of these effects may De linked to the same or closely overlapping the mesolimbic dopamine systems. Neiguan (PC6) point on the pericardium channel which is associated with the brain and its mental function, has been used to treat mental, psychosomatic disorders and gastroenterological disorders. The present study was designed to investigate the effect of acupuncture on repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and to measure the effect of acupuncture on repeated morphine-induced behavioral changes. Male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5 mg/kg, s.c.). Acupuncture was applied at bilateral Neiguan (PC6) points for 1min after the morphine challenge. Results showed that acupuncture at the specific acupoint PC6, but not at control points (tail and HE8) significantly decreased both dopamine release, behavior induced by a systemic morphine challenge or a single s.c. morphine injection in the morphine-repeated animals. These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts. Moreover, in a more general sense these results suggest that acupuncture can be used as a therapeutic intervention for correcting reversible malfunction of the body by direction of brain pathway and thus acupuncture can contribute to the biochemical balance in the central nervous system by regulating neurotransmitters.

• Applied Microscopy
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• v.32 no.3
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• pp.247-255
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• 2002

In this study, we carried out immunostaining and immunogold labeling with antibodies to serotonin and somatostatin to examine the characteristics and functions of the neurons that secrete neurotransmitters in optic lobes of Todarodes pacificus and Octopus minor. As a result of immunostaining with anti-somatostatin, the nerve cells of Todarodes pacificus reacted as similar to the anti-serotonin, but in Octopus minor, only large cells in the outer granule cell layer reacted positively. In the immunogold labeling with anti-serotonin, the nerve cells in the inner grande cell layer and medulla of Todarodes pacificus reacted strongly, 30 gold particles being labeled per $0.5{\mu}m^2$ of the cytoplasm. However, in Octopus minor, only 17 gold particles were labeled, which stated a weak reaction. On the other hand, in the anti-somatostatin case, the nerve cells in the outer and inner granule cell layers and medulla of Todarodes pacificus showed strong reaction, 30 gold particles being labeled per $0.5{\mu}m^2$ of the cytoplasm while the nerve cells in the outer granule cell layer of Octopus minor reacted weakly, about 3 gold particles being labeled per the equivalent area. As a result of immunostaining and immunogold labeling with two types of antibodies to each part of the optic lobes, we found that the reactive nerve cells were distributed differently in the two species. In particular, the degree of reactivity to the immunostaining and immunogold labeling appeared stronger in Todarodes pacificus than in Octopus minor.

• Applied Microscopy
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• v.32 no.2
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• pp.175-183
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• 2002

In this study, we carried out immunostaining and immunogold labeling with rabbit anti-dopamine (TH) and rabbit anti-calbindin-$D_{28K}$ to examine the characteristics and functions of the neurons that secrete neurotransmitters in optic lobes of Todarodes pacificus and Octopus minor inhabiting the Korean waters. The obtained results are as follow. In the immunostaining with anti-dopamine, only a few of the large amacrine cells in an the upper part of an outer granule cell layer and the cells forming the islands of medulla showed positive reaction in Todarodes pacificus, while $2{\sim}3$ cells in the upper and middle parts of an outer granule cell layer and more than 5 cells in the islands of medulla reacted positively in Octopus minor. For the case of anti-calbindin case, $2{\sim}3$ small amacrine cells in the upper portion of the outer granule cell layer and $1{\sim}2$ cells which are located in the lower part of an inner granule cell layer showed positive reaction in Todarodes pacificus, while, in Octopus minor, 4 cells in the outer granule cell layer reacted positively, no immunoreactive cell being found in the inner granule cell layer. As a result of performing the immunogold labeling, relative large number ($17{\sim}26$) of gold particles were labeled per $0.5{\mu}m^2$ of the cytoplasm of the cells which showed the immunoreactivity to the anti-dopamine and anti-calbindin in Todarodes pacificus, however, small number (10) of gold particles were labeled in Octopus minor, which reach only half of the number in the Todarodes pacificus.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.5
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• pp.207-213
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• 2007

This study was designed to characterize ureteral smooth muscle motility and also to study the effect of forskolin(FSK) and isoproterenol(ISO) on smooth muscle contractility in murine ureter. High $K^+$(50 mM) produced tonic contraction by $0.17{\pm}0.06mN$(n=19). Neuropeptide and neurotransmitters such as serotonin($5{\mu}M$), histamine($20{\mu}M$), and carbarchol(CCh, $10{\sim}50{\mu}M$) did not produce significant contraction. However, CCh($50{\mu}M$) produced slow phasic contraction in the presence of 25 mM $K^+$. Cyclopiazonic acid(CPA, $10{\mu}M$), SR $Ca^{2+}$-ATPase blocker, produced tonic contraction(0.07 mN). Meanwhile, inhibition of mitochondria by protonophore carbnylcyanide m-chlorophenylhydrazone(CCCP) also produced weak tonic contraction(0.01 mN). The possible involvement of $K^+$ channels was also pursued. Tetraethyl ammonium chloride(TEA, 10 mM), glibenclamide($10{\mu}M$) and quinidine($20{\mu}M$) which are known to block $Ca^{2+}$-activated $K^+$ channels($K_{Ca}$ channel), ATP-sensitive $K^+$ channels($K_{ATP}$) and nonselective $K^+$ channel, respectively, did not elicit any significant effect. However, $Ba^{2+}$($1{\sim}2mM$), blocker of inward rectifier $K^+$ channels($K_{IR}$ channel), produced phasic contraction in a reversible manner, which was blocked by $1{\mu}M$ nicardipine, a blocker of dehydropyridine-sensitive voltage-dependent L-type $Ca^{2+}$ channels($VDCC_L$) in smooth muscle membrane. This $Ba^{2+}$-induced phasic contraction was significantly enhanced by $10{\mu}M$ cyclopiazonic acid(CPA) in the frequency and amplitude. Finally, regulation of $Ba^{2+}$-induced contraction was studied by FSK and ISO which are known as adenylyl cyclase activator and $\beta$-adrenergic receptor agonist, respectively. These drugs significantly suppressed the frequency and amplitude of $Ba^{2+}$-induced contraction(p<0.05). These results suggest that $Ba^{2+}$ produces phasic contraction in murine ureteral smooth muscle which can be regulated by FSK and $\beta$-adrenergic stimulation.

• Archives of Pharmacal Research
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• v.26 no.10
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• pp.868-873
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• 2003

Ginsenosides, major active ingredients of Panax ginseng, that exhibit various pharmacological and physiological actions are transformed into compound K (CK) or M4 by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. Recent reports shows that ginsenosides might playa role as pro-drugs for these metabolites. In present study, we investigated the effect of bovine serum albumin (BSA), which is one of major binding proteins on various neurotransmitters, hormones, and other pharmacological agents, on ginsenoside $Rg_{2-}$, CK-, or M4-induced regulation of $\alpha3\beta4$ nicotinic acetylcholine (ACh) receptor channel activity expressed in Xenopus oocytes. In the absence of BSA, treatment of ACh elicited inward peak current ($I_{Ach}$) in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor. Co-treatment of ginsenoside $Rg_2$, CK, or M4 with ACh inhibited IAch in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor with reversible and dose-dependent manner. In the presence of 1% BSA, treatment of ACh still elicited $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor and co-treatment of ginsenoside $Rg_2$ or M4 but not CK with ACh inhibited $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor with reversible and dose-dependent manner. These results show that BSA interferes the action of CK rather than M4 on the inhibitory effect of $I_{Ach}$ in oocytes expressing $\alpha3\beta4$ nicotinic ACh receptor and further suggest that BSA exhibits a differential interaction on ginsenoside metabolites.

• Journal of Life Science
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• v.22 no.9
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• pp.1231-1236
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• 2012

Exercise leads to the release of certain neurotransmitters in the brain that alleviate pain, both physical and mental. The purpose of this study was to investigate effects of combined exercise on body composition, blood lipids, and brain-derived neurotrophic factor (BDNF) in overweight and obese adolescents. The subjects of this study were 18 boys who were divided into a combined exercise group (EG: n=9) and a control group (CG: n=9). The combined exercise program required exercise 50-60 minutes per day, three times a week, for 12 weeks. The results of the comparative analysis are as follows: The between-group comparison of the difference in the means before and after the intervention revealed a significant decrease in the EG compared with the CG: weight (p<0.01), BMI (p<0.05), %fat (p<0.05), fat mass (p<0.01). The %LBM of the EG showed a more significant increase (p<0.05) compared with the CG. The TC, LDL-C, and BDNF were not different between the EG and the CG. However, the TC and the LDL-C were decreased more in the EG than in the CG. The BDNF was increased more in the EG than in the CG. In conclusion, the combined exercise improved body composition but did not affect serum lipids or the BDNF.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.17 no.1
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• pp.152-158
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• 2016

Glutamate is one of the major excitatory neurotransmitters in the central nervous system of vertebrates. Human GDH (hGDH) is the enzyme that regulates the glutamate metabolism and its expression is higher in the brains of schizophrenia patients than in normal subjects. This study examined the changes in the hGDH enzymatic activity caused by antipsychotic drugs (haloperidol, risperidone, (${\pm}$)-sulpride, chlopromazine hydrochloride, melperone, (${\pm}$)butaclamol, domperidone, clozapine) related to schizophrenia. First of all, hGDH isozymes (hGDH1, hGDH2) were synthesized by genetic recombination. As a result of the enzyme assay, haloperidol, (${\pm}$)-sulpride, melperone and clozapine had an inhibitory effect on the hGDH isozymes. In addition, haloperidol showed a non-competitive inhibition against the substrate, 2-oxoglutarate. In contrast, it showed an uncompetitive inhibition against another substrate, NADH. The inhibitory effect of haloperidol on hGDH2 was abolished by the presence of L-leucine, an allosteric effector of hGDH, but by not other antipsychotic drugs. These results revealed the inhibition of enzyme activity by psychotropic drugs in hGDH isoenzymes (hGDH1 and hGDH2) and the possibility that haloperidol may be used to regulate the GDH activity and glutamate concentration in the central nervous system.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.179-194
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• 1995

This study aimed to determine whether exposure to stress during developmental period causes permanent behavioral and/or neurochemical alterations. Alterations of behavior were studied in young and aged rats which have been exposed to uncontrollable and unpredictable electric shocks on postnatal day(PND) 14 or PND 14 and 21. The concentrations of monoaminergic neurotransmitters were also measured to determine whether the behavioral alterations were accompanied by neurochemical changes. The results obtained are as follows: 1) The rate of increase in body weight was reduced at one day after exposure to the 1st series of shocks on PND14. However, these findings could not be observed after exposure to the 2nd series of shocks on PND 21. 2) Explorative activity decreased at one day after exposure to the 1st series of shocks on PND14. However this findings could not be observed after exposure to the 2nd series of shocks on PND 21. 3) At 100 days of age, there were little changes in the spontaneous locomotor activities measured for consecutive 23 hrs. However, there was positive correlation between the shock number showing the 1st helplessness during receiving the 1st series of shocks and the night time ambulatory activity of females, and was negative correlation between the shock number showing the 1st helplessness during receiving the 1st or 2nd series of shocks on PND 14 or 21 and the night time ambulatory activity of females. 4) At $360{\sim}390$ days of age, night time ambulatory activity decreased in female rats which have been exposed to shocks on PND 14 and 21, but not in males. 5) In the aged female rats, the concentrations of 5-HT, dopamine and their metabolites were not different among groups. However, the ratio of 5-HIAA/5-HT increased in the frontal cortices of rats exposed to shocks on PND 14 and 21. These results demonstrate that the early experience of serious stress results in persistent alterations of behavior accompanying altered neurochemistry, and aging may unmask a subtle neuronal deficit causes by the early experience of serious stress.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.153-164
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• 1995

Sympathomimetic amines, especially ephedrine, are a major ingredient in proprietary medications for symptomatic treatment of upper respiratory infections. Their frequent uses can lead to occasional instances of abuse and habituation. The clinical symptoms of ephedrine abuse are similar to that of amphetamine psychosis and resemble closely that of schizophrenia. Because both amphetamine psychosis and schizophrenia are thought to be mediated primarily through the action on catecholamines, ephedrine-induced changes of the biogenic amines can be suspected. However, there were few studies about the central effects of ephedrine because of the milder central action than peripheral. Therefore, the present investigation was undertaken to elucidate the relations between the effects of single or repeated administration of ephedrine on the regional levels of biogenic amines in rat brain and ephedrine-induced CNS stimulation. The male Sprague-Dawley rats weighing $100{\sim}200\;g$ were used. After single or repeated administrations of ephedrine, blocks of tissue were obtained from frontal cortex, corpus striatum, hippocampus, thalamus, hypothalamus, substantia nigra and cerebellum. The concentration of biogenic amines(norepinephrine, epinephrine, dopamine, 5-hydroxytryptamine(5-HT)) and their metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid(HVA), 5-hydroxyindoleacetic acid(5-HIAA)) were measured by means of high performance liquid chromatography-electrochemical detector(HPLC-ECD). The results obtained were as follows: 1) In the normal rat, the concentration of norepinephrine was the highest in hypothalamus. Dopamine, DOPAC and HVA were highest in corpus striatum, and 5-HT and 5-HIAA were highest in substantia nigra. Epinephrine was not detectable in any part of the brain tissue. 2) In a single administration of ephedrine, the concentration of DOPAC was decreased in corpus striatum. However, the other biogenic amines and their metabolites were not changed. 3) In repeated administration of ephedrine, the concentration of norepinephrine was decreased in all brain region checked. Dopamine was decreased in corpus striatum and substantia nigra and, increased in hypothalamus, and HVA was decreased in corpus striatum. 5-HT was decreased in all brain region except cerebellum and, 5-HIAA was decreased only in frontal cortex. The ratio of 5-HIAA/5-HT was increased in corpus striatum, thalamus, hypothalamus and substantia nigra. These data indicated that, although a single administration of ephedrine did not change the central neurotransmitters, repeated administration of ephedrine caused the decreases of norepinephrine and 5-HT in the most regions of brain, which may be responsible for the emergence of abnormal behavioral effect after ephedrine abuse.