• Korean Journal of Pharmacognosy
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• v.25 no.2
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• pp.194-197
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• 1994

MeOH extracts of sixteen herbal drugs were tested for the effects on bovine adrenal tyrosine hydroxylase and dopamine ${\beta}-hydroxylase$. The MeOH extracts of Paeoniae Radix and Pinelliae Tuber showed 65% inhibition on the tyrosine hydroxylase activity at the concentration of 100 $\mu$g in the enzyme reaction mixture. Those of Paeoniae Radix, Pinelliae Tuber and Evodiae Fructus showed 87, 84 and 62%, respectively, on the dopamine ${\beta}-hydroxylase$ activity.

• BMB Reports
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• v.29 no.5
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• pp.393-397
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• 1996

Sprague-Dawley male rats (150 g) were chronically treated with 5 v/v % ethanol admixed with nutritionally complete liquid diet and fed ad libitum for 3 weeks. Controls were pair fed with the isocaloric sucrose liquid diet. One half of each group was exposed to cold stress at $4^{\circ}C$ either for 24 h (for determination of mRNA by in situ hybridization) or for 48 h (for determination of enzyme activity). Chronic ethanol treatment (ethanol) did not affect tyrosine hydroxylase (TH) mRNA level in locus coeruleus (LC) of brain and adrenal medulla (AM) compared to controls. Cold stress showed strong increase of TH mRNA level in LC and AM compared to controls. Pretreated ethanol reduced the increased TH mRNA level by cold stress in LC and AM. Ethanol did not affect TH activity in LC and adrenal glands (adrenals). Cold stress increased TH activity in LC but not in adrenals. Pretreated ethanol did not reduce the increased TH activity by cold stress in LC but this result was not shown in adrenals. It is suggested that ethanol does not affect the message level and enzyme protein level for TH in LC and AM in normal rat. It is also hypothesized that pretreated ethanol reduces the magnitude of acute cold stress response, that is induction of TH mRNA in LC and AM, and does not reduce the increased TH enzyme protein that is also acute cold stress response in LC.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.1-5
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• 1991

We studied changes in the hypothalamic norepinephrine(NE) metabolism in streptozotocin (STZ)-induced diabetic rats by measuring basal NE levels, turnover rate of NE, and in vivo tyrosine hydroxylase activities. Basal NE level did not change significantly upto 4 weeks after the establishment of diabetes with STZ(60 mg/kg, iv). But turnover rate of NE decreased to 62% of control rate(P<0.01), and in vivo tyrosine hydroxylase activities decreased to 32% of control level(P<0.05) at one week of diabetes. From these results, we concluded that, of the three parameters measured, in vive tyrosine hydroxylase activity is the most sensitive index of altered hypothalamic NE metabloism in STZ-induced diabetic rats.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.258-260
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• 1996

Palmatine, an protoberberine isoquinoline alkaloid, has been found to inhibit dopamine biosynthesis by reducing tyrosine hydroxylase (TH) activity in PC12 cells (Lee and Kim, 1996). We have therefore investigated the effects of palmatine on bovine adrenal TH. Palmatine showed a mild inhibition on bovine adrenal TH (36.4% inhibition at concentration of $200\muM$). Bovine adrenal TH was inhibited competitively by palmatine with a substrate L-tyrosine. The Ki value was found to be 0.67 mM. This result suggests that the inhibition of TH activity by palmatine may be partially involved in the reduction of dopamine biosynthesis in PC12 cells.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.782-784
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• 1998

Ginseng total saponin (GTS) can modulate dopaminergic activity at both presynaptic and postsynaptic dopamine receptors (Kim et al, 1998). The present study investigated t he effect of GTS on the bovine adrenal tyrosine hydroxylase (TH), which catalyze L/tyrosine to DOP. GTS inhibited the bovine adrenal TH by 42.4, 51.5 and 55.3% at concentrations of 40, 80 and 100${\mu}g$/ml, respectively. The IC50 value of GTS was 77.5${\mu}g$/ml. GTS exhibited noncompetitive inhibition with a substrate L-tyrosine. The Ki value was 155${\mu}g$/ml.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.7-12
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• 1991

We measured the developmental increase of tyrosine hydroxylase(TH) activity and dopamine content with high performance liquid chromatography with electrochemical detection(HPLC-EC) in dissociated cultures of fetal rat brainstem(E14). TH activity and dopamine content increased progressively upto 7 days in vitro, when the effects of various drugs on the dopamine contents were studied. ${\alpha}-Methyl-p-tyrosine$, a TH inhibitor and NSD-1015, an inhibitor of aromatic amiono acid decarboxylase effectively depleted dopamine contents. Dopamine contents were depleted by reserpine and increased by pargyline. When cultures grown for 1 week in control medium were then exposed to tetrodotoxin$(0.1\;{\mu}M$) for 7 days, exposure to tetrodotoxin markedly decreased TH activity. All the above results indicate that dopamine metabolism in the cultered cells reflect reliably the property of brain dopamine metabolism. We suggest that measuring TH activity and dopamine content in brainstem culture with HPLC-EC can be useful tool in the study of pharmacology as well as toxicology of the central dopaminergic system.

• Molecules and Cells
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• v.44 no.7
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• pp.493-499
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• 2021

Parkinson's disease (PD) is characterized by a progressive loss of dopamine-producing neurons in the midbrain, which results in decreased dopamine levels accompanied by movement symptoms. Oral administration of l-3,4-dihydroxyphenylalanine (L-dopa), the precursor of dopamine, provides initial symptomatic relief, but abnormal involuntary movements develop later. A deeper understanding of the regulatory mechanisms underlying dopamine homeostasis is thus critically needed for the development of a successful treatment. Here, we show that p21-activated kinase 4 (PAK4) controls dopamine levels. Constitutively active PAK4 (caPAK4) stimulated transcription of tyrosine hydroxylase (TH) via the cAMP response element-binding protein (CREB) transcription factor. Moreover, caPAK4 increased the catalytic activity of TH through its phosphorylation of S⁴⁰, which is essential for TH activation. Consistent with this result, in human midbrain tissues, we observed a strong correlation between phosphorylated PAK4^S474, which represents PAK4 activity, and phosphorylated TH^S40, which reflects their enzymatic activity. Our findings suggest that targeting the PAK4 signaling pathways to restore dopamine levels may provide a new therapeutic approach in PD.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.510-512
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• 1997

The effects of noscapine a phthalide isoquinoline alkaloid, on dopamine biosynthesis and tyrosine hydroxylase (TH) activity in PC12 cells were investigated. Noscapine showed 74.6% inhibition on dopamine content in PC12 cells at a concentration of $20{\mu}M.$ $IC_{50}$ of noscapine was $6.8{\mu}M.$ TH activity was inhibited by the treatment of noscapine in PC12 cells (20.9% inhibition at 20 .mu.M). Therefore, the inhibition of TH activity by noscapine might be involved in at least one component of the reduction of dopamine biosynthesis in PC12 cells.

• Korean Journal of Pharmacognosy
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• v.26 no.1
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• pp.57-61
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• 1995

MeOH extracts of eight herbal medicines were investigated for the effects on catecholamine biosynthesis and tyrosine hydroxylase (TH) activity in PC12 cells. Among them, the MeOH extracts of Polygalae Radix and Rehmaniae Radix showed 32 and 22% inhibition on the dopamine biosynthesis, respectively at a concentration of $40{\mu}g/ml$ medium. But, the TH activity was reduced by the treatment of Polygalae Radix. These results suggest that Polygalae Radix has an inhibitory effect on the catecholamine biosynthesis by the reduction of TH activity in PC12 cells.

• Natural Product Sciences
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• v.10 no.3
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• pp.114-118
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• 2004

It is reported that $(1R,9S)-{\beta}-Hydrastine$ hydrochloride (BHSH) decreased the intracellular dopamine content by inhibiting tyrosine hydroxylase (TH) activity in PC12 cells. In this study, the inhibitory mechanisms on TH activity by BHSH in PC12 cells were investigated. BHSH treatment caused a reduction of TH activity and TH mRNA level in a dose-dependent manner. After the treatment of $20\;{\mu}M$ BHSH, TH activity and TH mRNA content were reduced at 15 min, reached the minimal levels at 6-24 h, and then recovered gradually to the control level. BHSH at $10-50\;{\mu}M$ caused a decrease in the basal intracellular cyclic AMP levels at 10 min in a concentration-dependent manner. In addition, BHSH at $20-100\;{\mu}M$ decreased the basal intracellular $Ca^{2+}$ concentration $([Ca^{2+}]_i)$ immediately in a dose-dependent manner. BHSH also inhibited the 56 mM $K^+ $ depolarization-induced elevation in $[Ca^{2+}]_i$, and blocked caffeine-activated store-operated $Ca^{2+}$ entry in PC12 cells. These data suggest that BHSH inhibits TH activity and TH gene expression, in part, through reducing cyclic AMP content and basal $[Ca^{2+}]_i$ in PC12 cells.