• 분석과학
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• 제28권2호
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• pp.98-105
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• 2015

버얼리종 담배에서 추출물에서 얻은 peroxidase와 다중벽 탄소 나노튜브를 이용한 dopamine 정량 바이오센서를 만들었다. Peroxidase는 dopamine을 dopamine quinone으로 산화시키는 반응의 촉매 역할을 한다. 이 논문은 효소의 농도, pH와 같은 바이오센서의 감응에 영향을 주는 parameter를 조사하였다. 또한, 전극의 감도, 직선성의 범위, 전극의 안정성을 조사하였다. 본 실험에 사용한 dopamine의 정량 센서는 pH 6.50, 0.010 M 인산 완충용액, -0.15 V의 가해준 전압에서 가장 좋은 감응을 나타내었다. 전극의 검출한계(S/N ＝3)는 2.7×10⁻⁶ M이었으며, 5.0×10⁻² M dopamine을 이용하여 10회 반복 측정한 상대표준편차는 1.3%이었다.

• 대한약리학회지
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• 제27권1호
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• pp.7-12
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• 1991

쥐(태령 14일) 뇌간 세포배양에서 발달과정에 따른 Tyrosine hydroxylase(TH) 활성 및 dopamine의 양적 증가를 전기화학 HPLC를 이용하여 측정하였다. TH 활성 및 dopamine의 양은 배양 7일까지 점차 증가하였다. 배양 7일째에 여러 약물들의 dopamine 대사에 대한 영향을 조사하였다. TH 억제제인 ${\alpha}-methyl-p-tyrosine$ 및 aromatic amiono acid decarboxylase 억제제인 NSD-1015는 효과적으로 dopamine을 고갈시켰다. Dopamine은 reserpine에 의해 고갈되었고, parglyine에 의해 증가되었다. 일주일 배양한 세포의 배양액에 tetrodotoxin$(0.1\;{\mu}M$)을 7일간 투여하였을 때 TH 활성은 현저히 감소하였다. 이상의 결과들은 배양세포의 dopamine 대사가 뇌 dopamine 대사를 충실히 반영함을 나타낸다. 뇌간 세포의 배양에서 HPLC-전기화학검출을 이용한 TH 활성 및 dopamine의 측정은 중추 dopamine계의 약리 및 독성 연구에 유용하리라 사료된다.

• Biomolecules & Therapeutics
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• 제10권3호
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• pp.152-158
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• 2002

The present study elucidated the effect of $\beta$-carbolines (harmaline and harmalol) on brain mitochondlial dysfunction caused by the tyrosinase-induced oxidation of dopamine. Harmaline, harmalol and antioxidant enzymes (SOD and catalase) attenuated the dopamine-induced alteration of membrane potential, cytochrome c release and thiol oxidation in mitochondria. In contrast, antioxidant enzymes failed to reverse mitochondrial dysfunction induced by dopmnine plus tyrosinase. $\beta$-Carbolines decreased the damaging effect of dopamine plus tyrosinase against mitochondria, except no effect of harmalol on thiol oxidation. Antioxidant enzymes decreased the melanin formation from dopamine in the reaction mixture containing mitochondria but did not reduce the formation of dopamine quinone caused by tyrosinase. Both harmalol and harmaline inhibited the formation of reactive quinone and melanin. Harmalol being more effective for quinone formation and vise versa. The results indicate that compared to MAO-induced dopamine oxidation, the toxic effect of dopamine in the presence of tyrosinase against mitochondria may be accomplished by the dopamine quinone and toxic substances other than reactive oxygen species. $\beta$-Carbolines may decrease the dopamine plus tyrosinase-induced brain mitochondrial dysfunction by inhibition of the formation of reactive quinone and the change in membrane permeability.

• 약학회지
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• 제39권2호
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• pp.161-168
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• 1995

Brain dopamine systems play a central role in the control of movement, hormone release, and many complex behavior. The action of dopamine at its synapse is terminated predominately by high affinity reuptake into presynaptic terminals by dopamine transporter (DAT). The dopamine transporter(DAT) is membrane protein localized to dopamine-containing nerve terminals and closely related with cocaine abuse, Parkinsonism, and schizophrenia. In present study, the recombinant plasmid pRc/CMV-DAT, constructed by subcloning of a cDNA encoding a bovine DAT into eukaryotic expression vector pRc/CMV, was stably transfected into CV-1 cells(monkey kidney cell line). The DAT activities in the cell lines selected by Geneticin$^{R}$ were determined by measuring the uptake of $[^3H]$-dopamine. The transfected cell lines showed 30-50 fold higher activities than untransfected CV-1 cell line, and this result implies that DAT is well expressed and localized in transfected cells. The transfected cells accumulated $[^3H]$-dopamine in a dose-dependent manner with a $K_{m}$ of 991.6nM. Even though high doses of norepinephrine, epinephrine, serotonin, and choline neurotransmitters inhibited the uptake of $[^3H]$-dopamine, DAT in transfected cell line was proven to be much more specific to dopamine. The psychotropic drugs such as GBR12909, CFT, normifensine, clomipramine, desipramine, and imipramine inhibited significantly the dopamine uptake in tissue culture cells stably transfected with DAT cDNA. Radioactive in situ hybridization was done to map the cellular localization of DAT mRNA-containing cells in the adult rat central nervous system. The strong hybridization signals were detected only in the substantia nigra pars compacta and ventral tegmental area. The restricted anatomical localization of DAT mRNA-containing cells confirms the DAT as a presynaptic marker of dopamine-containing cells in the rat brain.

• The Korean Journal of Physiology
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• 제20권1호
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• pp.9-15
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• 1986

위(胃) 전기활동(서파)의 전파(傳播) 및 발생빈도에 미치는 dopamine의 영향을 주명하기 위하여 145마리의 고양이를 사용하며 다음의 실험을 실시하였다. 위의 복측부분을 적출하여 종주근의 주행 방향으로 대만쪽에서 길이 5cm, 폭 1.2cm인 근절편을 만들어, 95% $O_2$와 5% $CO_2$가 계속 공급되는 Krebs-Ringer용액 (PH 7.4, 온도 $36{\pm}0.5^{\circ}C$)내에 두고 가느다란 은선이 들어있는 모세관 전극 (Ag-AgCl)을 사음하여 단극성으로 서파를 기록하였다. dopamine의 첨가후 위서파의 전파방향은 첨가한 농도에 비례하여 전환이 많아졌으나, dopamine의 영향은 domperidone의 전처치로 유의하게 억제되었다. dopamine은 또한 농도가 증가함에 따라 불규칙한 위서파의 발생만도를 증가시켰으며 이 현상은 domperidone 및 Phentolamine에 의하여 억제되었으나 Propranolol, hexamethonium 및 tetrodotoxin에 의하여는 억제되지 않았다. 그러므로 dopamine은 고양이 위에서 dopamine receptor와 일부 ${\alpha}-adrenergic\;receptor$에 작용하며 이상적(異常的)서파를 발생시킨다고 사료된다.

• Toxicological Research
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• 제6권1호
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• pp.75-88
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• 1990

The characteristics of dopamine uptake, D-1 and D-2 receptors after acute and subacute cocaine administration were determind in striatum from WKY and SHR. Cocaine was administered either acutely (40 mg/kg, s.c.) or twice daily (20 mg/kg, s.c.) for 3 and 7 days in 9-wk old WKY and SHR. Rats were sacrificed 30 min, 2 or 24 h after the single injection and 18 h after the last administration to the subacutely treated group. The changes in dopamine uptake, dopamine uptake sites, D-1 and D-2 receptors were determined using $(^3H)$dopamine, $(^3H)$-GBR-12935, $(^3H)$SCH-23390 and $(^3H)$sulpiride, respectively. In acutely treated rats, significant increases in $V_{max}$of dopamine uptake were observed 30 min after the cocanine injection in both strains without changes in $K_m$ values. The in vitro $IC_{50}$for cocaine was significantly decreased 30 min in WKY and 2 h in SHR. However, that for in vitro GBR-12909 was significantly increased 30 min and 2 h in both strains. Also densities of $(^3H)$-GBR-12935 binding sites were significantly increased 30 min and 2 h without changes in their $K_d$. Significant increases in D-2 receptor density were observed 30 min, 2 or 24 h after acute injection in both strains without changes in their affinities. The density of D-1 receptor was significantly decreased 30 min after the injection in WKY, but not in SHR. In subacutely treated rats, a significant increase in $K_m$ of dopamine uptake was observed in 7-day treated SHR. The in vitro $IC_{50}$fot GBR-12909 was significantly increased in 3-day treated WKY. The density of D-1 receptors was significantly increased in 3- and 7-day treated WKY, but not in SHR. The affinity of both binding sites remained unchanged. The results suggest that cocanine administration alters dopamine uptake, characteristics of dopamine uptake sites and dopamine receptor binding characteristics in rat brain. Furthermore, D-1 and D-2 dopamine receptors appear to be differently regulated.

• The Korean Journal of Physiology
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• 제17권2호
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• pp.103-107
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• 1983

This experiment was undertaken to see whether dopamine has any effect on a uterine function and whether the uterus has a dopamine receptor. We used 14 female rats in the diestrus state which was identified by a vaginal smear. Under ether anesthesia, 3 pieces(1 cm length) from each side of the uterus were dissected out and mounted in 3 tissue chambers (4 cm diameter, 10 cm height) that contained Krebs-Ringer solution. The solution was continuously aerated with 95% $O_2$ containing 5% $CO_2$ and kept $37^{\circ}C$ consistantly during the whole experimental period. The spontaneous contractile activity of the isolated uterus was recorded using a force transducer. After a recovery period of 15 min in the chamber, the following experiments were carried out. In 7 rats, each piece of the uterus was received dopamine at concentrations of $10^{-4}$, $10^{-5}$ or $10^{-6}\;M$ for 10 min and then followed by domperidone at a concentration of $10^{-5}\;M$. In another 7 rats, each piece was received domperidone, a specific peripheral dopamine receptor antagonist, was administered at a concentration of $10^{-5}\;M$ for 5 min prior to dopamine at concentrations of $10^{-4}$, $10^{-5}$, or $10^{-6}\;M$. Dopamine inhibited the spontaneous uterine contraction dose-dependently (r=0.99, p<.01). The inhibited contractility by dopomine was significantly (P<.05) resumed by post-treatment of domperidone. Pre-treatment of domperidone also blocked significantly(p<.05) the inhibitory effect of dopamine. It is concluded from these results that dopamine has inhibitory role upon the spontaneous uterine contraction of the rat in the diestrus state and domperidone antagonized the inhibitory effect of dopamine. These results suggest strongly that dopamine may exert the inhibitory effect via the dopamine receptor in the rat uterus.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.97-97
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• 2001

This Study was attempted to investigate tile effect of dopamine, SKF 81297, a dopamine D$_1$-receptor agonist, and TNPA, a dopamine D$_2$-receptor agonist, on the blood pressure in rat. Dopamine exhibited the hypertensive action in proportion to the doses of 1.0, 3.0 arid 10.0 $\mu\textrm{g}$/kg i.v., these hypertensive action of dopamine was blocked significantly by SCH 23390, a dopamine D$_1$-receptor antagonist, on the other hand, more potentiated by raclopride, a dopamine D$_1$-receptor antagonist. SKF 81297 produced hypertensive action in a dose of 1.0 $\mu\textrm{g}$/kg i.v., wherease hypotensive action in proportion to administered doses 3.0 and 10.0 $\mu\textrm{g}$/kg i.v., these hypertensive action of SKF 81297 in a dose of 1.0 $\mu\textrm{g}$/kg i.v. was not influenced by SCH 23390 or raclopride, but hypotensive action of SKF 81297 in tile doses of 3.0 and 10.0 $\mu\textrm{g}$/kg i.v. was weakened significantly by SCH 23390, but more strenthened by raclopride. TNPA showed the hypotensive action in inverse proportion to administered doses of 1.0, 3.0 and 10.0 $\mu\textrm{g}$/kg i.v., these hypotensive action was reversed to hypertensive action in inverse proportion to the administered doses of TNPA by SCH 23390 and raclopride.

• 생물정신의학
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• 제12권2호
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• pp.107-113
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• 2005

Purpose:In an attempt to predict the interpersonal differences of therapeutic response to antipsychotic drugs on pharmaco-genetic bases, this study was designed to investigate the relationship between the therapeutic response to antipsychotic drugs and Taq I A dopamine $D_2$ receptor polymorphism in schizophrenic patients. Methods:The subjects were 158 patients diagnosed with schizophrenia(DSM-IV). The therapeutic response to antipsychotic drugs was evaluated using the Treatment Response Scale(TRS) retrospectively. Patients were divided into two groups, dopamine receptor antagonist responders, and serotonin-dopamine antagonist responders. The patients' Taq I A dopamine $D_2$ receptor polymorphism was determined by polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP). Results:The dopamine receptor antagonist responders had the A1 allele in significantly higher incidences (${\chi}^2$(1)=4.875, p=0.027, two-tailed). No significant difference was found among the serotonin-dopamine antagonist responders between those with or without the A1 allele. Conclusions:The patients with the A1 allele responded better to dopamine receptor antagonists than those with no A1 allele. Based on these results, it is suggested that the pharmacological effect of dopamine receptor antagonists can be predicted depending on the presence of the A1 allele in schizophrenic patients.

• Biomolecules & Therapeutics
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• 제12권1호
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• pp.9-18
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• 2004

Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of ${\beta}$-carbolines (harmaline and harmalol) and deprenyl on the dopamine-induced change in the mitochondrial membrane permeability and cell death in differentiated PC12 cells. Cell death due to 250 4{\mu}$M dopamine was inhibited by caspase inhibitors (z-IETD.fmk, z-LEHD.fmk and z-DQMD.fmk) and antioxidants (N-acetylcysteine, ascorbate, superoxide dismutase, catalase and carboxy-PTIO). ${\beta}$-Carbolines prevented the dopamine-induced cell death in PCl2 cells, while deprenyl did not inhibit cell death. ${\beta}$-Carbolines decreased the condensation and fragmentation of nuclei caused by dopamine in PC12 cells. ${\beta}$-Carbolines inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, formation of reactive oxygen species and depletion of GSH caused by dopamine in PC12 cells, whereas deprenyl did not decrease dopamine-induced mitochondrial damage. ${\beta}$-Carbolines, deprenyl and antioxidants depressed the formation of nitric oxide and melanin in dopamine-treated PC12 cells. The results suggest that cell death due to dopamine PC12 cells is mediated by caspase-8, -9 and -3. Unlike deprenyl, ${\beta}$-carbolines may attenuate the dopamineinduced cell death in PC12 cells by suppressing change in the mitochondrial membrane permeability through inhibition of the toxic action of reactive oxygen and nitrogen species.