• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.106-112
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• 2008

The effects of harman and norharman on dopamine content and L-DOPA-induced cytotoxicity were investigated in PC12 cells. Harman and norharman decreased the intracellular dopamine content for 24 h. The $IC_{50}$ values of harman and norharman were 20.4 ${\mu}M$ and 95.8 ${\mu}M$, respectively. Tyrosine hydroxylase (TH) activity and TH mRNA levels were also decreased by 20 ${\mu}M$ harman and 100 ${\mu}M$ norharman. Under the same conditions, the intracellular cyclic AMP levels were decreased by harman and norharman. In addition, harman and norharman at concentrations higher than 80 ${\mu}M$ and 150 ${\mu}M$ caused cytotoxicity at 24 h in PC12 cells. Non-cytotoxic ranges of 10-30 ${\mu}M$ harman and 50-150 ${\mu}M$ norharman inhibited L-DOPA (20-50 ${\mu}M$)-induced increases of dopamine content at 24 h. Harman at 20-150 ${\mu}M$ and norharman at 100-300 ${\mu}M$ also enhanced LDOPA (20-100 ${\mu}M$)-induced cytotoxicity at 24 h. These results suggest that harman and norharman decrease dopamine content by reducing TH activity and aggravate L-DOPA-induced cytotoxicity in PC12 cells.

• Annals of Clinical Neurophysiology
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• v.10 no.2
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• pp.98-100
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• 2008

Restless legs syndrome (RLS) is a sensorimotor neurological disorder in which the primary symptom is a compelling urge to move the legs, accompanied by unpleasant and disturbing sensations in the legs. Although pathophysiologic mechanism of RLS is still unclear, several evidences suggest that RLS is related to dysfunction in central nervous system involving brain and spinal cord. L-DOPA, as the precursor of dopamine, as well as dopamine agonists, plays an essential role in the treatment of RLS leading to the assumption of a key role of dopamine function in the pathophysiology of RLS. Patients with RLS have lower levels of dopamine in the substantia nigra and respond to iron administration. Iron, as a cofactor in dopamine production, plays a central role in the etiology of RLS. Functional neuroimaging studies using PET and SPECT support a central striatal D2 receptor abnormality in the pathophysiology of RLS. Functional MRI suggested a central generator of periodic limb movements during sleep (PLMs) in RLS. However, to date, we have no direct evidence of pathogenic mechanisms of RLS.

• Korean Journal of Biological Psychiatry
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• v.25 no.1
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• pp.16-20
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• 2018

Objectives Psychological resilience is the ability to cope with stress. The genetic background behind psychological resilience is not much known. The serotonin transporter and dopamine transporter are implicated in stress related psychology and emotional processing. The aim of this study is to investigate a possible genetic role of functional polymorphisms of serotonin and dopamine transporters for psychological resilience. Methods A total of 951 healthy adult subjects were included. Psychological resilience was measured using Connor-Davidson Resilience Scale (CD-RISC). Genotyping was performed for serotonin transporter gene(SERT) promoter variable number tandem repeat (VNTR) and dopamine transporter gene(DAT1) 3'-untranslated region (UTR) VNTR. Genetic association analysis was conducted between genotypes and the CD-RISC score. Results No genetic association was observed for SERT promoter VNTR or DAT1 3'-UTR VNTR with CD-RISC score. No genetic interaction between SERT promoter VNTR and DAT1 3'-UTR VNTR with CD-RISC score was detected. Conclusions Either serotonin or dopamine transporter did not seem to play a significant role for psychological resilience in this sample.

• Korean Journal of Pharmacognosy
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• v.29 no.4
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• pp.265-270
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• 1998

The effects of MeOH extracts of ninety kinds of medicinal herbs on dopamine content in PC12 cells were investigated. Among them, the MeOH extracts at a concentration of $40\;{\mu}g/ml$ of Symplocarpus renifolius, Adenocaulon himalaicum and Mosla punctulata decreased $38.5{\sim}60.0%$ of dopamine content. Tyrosine hydroxylase, the rate-limiting enzyme of the catecholamine biosynthesis, was inhibited by the treatment of the MeOH extracts of Symplocarpus renifolius, Adenocaulon himalaicum and Mosla punctulata ($19.9{\sim}31.3%$ inhibition at $40\;{\mu}g/ml$). These results suggested that these bioactive herbal medicines exhibited partially an inhibitory effect on dopamine biosynthesis by the reduction of tyrosine hydroxylase activity in PC12 cells.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.218-224
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• 1997

The results regarding an association between the polymorphism sites in the dopamine $D_1$ receptor gene and schizophrenia compelled us to study the distribution of the polymorphism in Korean schizophrenia and controls. Eighty-eight schizophrenic patients and normal controls were examined by case-control study for distribution of the polymorphism of the dopamine $D_1$ receptor gene in Korean popualtion to minimize the effect of racial differencies in gene frequencies. The frequencies of the $B_1$ and $B_2$ in schizophrenic patients were 0.11 and 9.89, respectively. And 0.10 and 0.90 in normal control. Ther was no significant differences in the frequencies in the allele $B_1$ and $B_2$between schizophrenic patients and normal controls. The author present here the evidence of a lack of alleic association between the polymorphism of the dopamine $D_1$ receptor gene and Korean schizophrenic patients. The assumption that the dopamine $D_1$ receptor gene has a genetic role in the development of schizophrenia was not suppoorted by this case-control study.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.19 no.1
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• pp.19-27
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• 2008

Objectives : The aim of this study was to examine the association of attention-deficit hyperactivity disorder (ADHD) in Korean populations with functional polymorphisms of six genes dopamine receptors (Ser311/Cys311 polymorphism, Taq1 A polymorphism, and Taq1 B polymorphism in DRD2, BalI polymorphism in DRD3, and promoter -521 C/T polymorphism and exon III 48 bp repeat polymorphism in DRD4) and one gene in dopamine transporter (DAT1). Methods : Participants were 58 children with ADHD and 110 control children. The genotypes were determined by PCR. Results : There was a statistically significant difference in genotype frequency of -521 C/T polymorphism within the promoter region of the DRD4 between two groups. Furthermore, in the male group, both genotype and allele frequencies showed statistically significant differences. Conclusion : Findings of the study indicate that -521 C/T polymorphism in promoter region of DRD4 appears to be a possible candidate gene for ADHD in Korean population.

• Natural Product Sciences
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• v.20 no.4
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• pp.296-300
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• 2014

The present study investigated the effects of (-)-sesamin on dopamine biosynthesis in PC12 cells. Treatment with (-)-sesamin (25 and $50{\mu}M$) increased intracellular dopamine levels and enhanced L-DOPA-induced increase in dopamine levels in PC12 cells. (-)-Sesamin (25 and $50{\mu}M$) also induced the phosphorylation of cyclic AMP-dependent kinase A (PKA), cyclic AMP-response element binding protein (CREB) and tyrosine hydroxylase (TH) in PC12 cells. These results suggest that (-)-sesamin induces dopamine biosynthesis via the PKA-CREB-TH pathways in PC12 cells. (-)-Sesamin needs to be studied further to serve as an adjuvant phytonutrient in neurodegenerative disease.

• Natural Product Sciences
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• v.24 no.2
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• pp.99-102
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• 2018

This study investigated the effects of ombuoside, a flavonol glycoside, on dopamine biosynthesis in PC12 cells. Ombuoside at concentrations of 1, 5, and $10{\mu}M$ increased intracellular dopamine levels at 1 - 24 h. Ombuoside (1, 5, and $10{\mu}M$) also significantly increased the phosphorylation of tyrosine hydroxylase (TH) (Ser40) and cyclic AMP-response element binding protein (CREB) (Ser133) at 0.5 - 6 h. In addition, ombuoside (1, 5, and $10{\mu}M$) combined with L-DOPA (20, 100, and $200{\mu}M$) further increased intracellular dopamine levels for 24 h compared to L-DOPA alone. These results suggest that ombuoside regulates dopamine biosynthesis by modulating TH and CREB activation in PC12 cells.

• YAKHAK HOEJI
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• v.52 no.6
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• pp.488-493
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• 2008

2-Aminothiazole ring as a bioisoster of catechol in dopamine has provided with good oral availability and lipophilic property. 2-Aminoindan, is a rigid form of dopamine, was evaluated as a dopamine D3 agonist with low neurotoxicity. Dopamine D3 agonist was evaluated as selective for the treatment of Parkinson's disease. In order to develop a novel dopamine D3 agonist, we tried to synthesize the aminothiazoloindenoxazine derivative that is a hybrid structure of aminoindenoxazine and thiazole ring. cis-2-Amino-1-indanol (2) was synthesized from 1,2-indandione-2-oxime by catalytic hydrogenation and it was treated with chloroacetyl chloride and NaH in benzene solution to give (${\pm}$)-cis-4,4a,5,9b-tetrahydroindeno[1,2-b][1,4]oxazin-3(2H)-one (6). Nitration of 6 by the mixed acid gave 8-nitro compound (7) and the carbonyl group of 7 was reduced with $LiAlH_4$ to afford compound (8). 8 was reduced to form (${\pm}$)-cis-8-amino-2,3,4,4a,5,9b-hexahydroindeno[1,2-b][1,4]oxazine (9) and finally it was cyclized with KSCN in glacial acetic acid to yield (${\pm}$)-cis-8-amino-2,3,4,4a,5,10b-hexahydrothiazolo[4,5-f]indeno[1,2-b][1,4]oxazine (10).

• Archives of Pharmacal Research
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• v.19 no.1
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• pp.23-29
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• 1996

Changes in dopaminergic activities were investigated after the intracerebroventricular (icv) administration of ethylcholine aziridium (AF64A) in rats. The levels of dopamine (DA) and metabolites, the activities of tyrosine hydroxylase (TH) and monoamine oxidase (MAO), and the specific binding sites of dopamine receptros in striata, hippocampus, and frontal cortex were assessed 6 days after the AF64A treatment with 3 nmol/each ventrcle. In frontal cortex, the levels of DA and metabolities were significantly decreased without changes in metabolites/DA ratios in the AF64A-treated groups. In contrast, the ratios of metabolites/DA were significantly decreased in striatum and hippocampus in the AF64A treatment. The activity of TH in frontal cortex was significantly decreased. However, that in other areas was not changed. Also the activity of MAO-A was not changed in the studied brain regions. However, the activity of MAO-B in striatum was significantly increased with no change in other areas. The specific binding sites of dopamine D1 and D2 receptors were increased in AF64A-treated frontal cortex. However, those were not changed in striatum and hippocampus except the small decreased specific binding sites of dopamine D-1 receptors in striatum after AF64A treatment. These results indicate that the dopaminergic activity was altered in AF64A treatment. Furthermore, it suggest that the decreased dopaminergic activities in each brain regions might be differently affected by AF64A treatment.