• 생약학회지
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• 제25권2호
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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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• 제29권5호
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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.

• 대한약리학회지
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• 제27권1호
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• pp.1-5
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• 1991

Streptozotocin(STZ)-유발 당뇨쥐에서 시상하부의 norepinephrine(NE) 대사를 기초 NE 함량, NE 교체율, in vivo tyrosine hydroxylase(TH) 활성을 그 지표로 하여 조사하였다. STZ (60 mg/kg, iv)로 당뇨를 유발한 후 4주까지 기초 NE 함량은 유의한 변화가 없었다. 그러나 당뇨유발 후 1주째에 측정한 NE 교체율은 대조치의 62%(p<0.01), in vivo TH 활성은 대조치의 34% (p<0.05)로 감소하였다. 이상의 결과로 본 실험에서 측정한 NE 대사의 세 지표 중에서 in vivo TH 활성이 STZ-유발 당뇨쥐의 시상하부 NE 대사의 변화를 가장 민감하게 반영하였다.

• Archives of Pharmacal Research
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• 제19권4호
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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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• 제21권6호
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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.

• 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.

• Molecules and Cells
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• 제44권7호
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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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• 제20권5호
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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.

• 생약학회지
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• 제26권1호
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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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• 제10권3호
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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.