• 제목/요약/키워드: dopamine

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Tetrahydropapaveroline의 PC12 세포내 Dopamine 생합성 저해작용 (Inhibitory Effects of Tetrahydropapaveroline on Dopamine Biosynthesis in PC12 Cells)

  • 이재준;김유미;김미나;이명구
    • 약학회지
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    • 제49권2호
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    • pp.156-161
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    • 2005
  • Tetrahydropapaveroline (THP) at 5-15 ${\mu}$M has been found to induce L-DOPA-induced oxidative apoptosis in PC12 cells. In this study, the inhibitory effects of THP on dopamine bios ynthesis in PC12 cells and tyrosine hydroxylase (TH) activity in bovine adrenal were investigated. Treatment of PC12 cells with THP at 2.5-10 ${\mu}$M significantly decreased the intracellular dopamine content in a concentration-dependent manner (18.3% inhibition at 10 ${\mu}$M THP). In these conditions, TH activity was markedly inhibited by the treatment with THP at 2.5-10 ${\mu}$M in PC12 cells (23.4% inhibition at 10 $\mu$ M THP). In addition, THP had an inhibitory effect on bovine adrenal TH activity IC50 value, 153.9${\mu}$M). THP exhibited uncompetitive inhibition on bovine adrenal TH activity with a substrate L-tyrosine with the KI value of 0.30 mM. Treatment with L-DOPA at 20~50 ${\mu}$M increased the intracellular dopamine content in PC12 cells, and the increase in dopamine content by L-DOPA was inhibited in part when THP at non-cytotoxic (5-10 ${\mu}$M) or cytotoxic (15${\mu}$M) concentrations was associated with L-DOPA (20 and 50 ${\mu}$M) for 24 h incubation. These results suggest that THP at 5-10${\mu}$M decreases the basal dopamine content and reduces the increased dopamine content induced by L-DOPA in part by the inhibition of TH activity, and that THP at 15${\mu}$M also decreases dopamine content by oxidative stress in PC12 cells.

정신분열병의 병태생리 및 치료영역에서의 serotonin의 역할 (Role of Serotonin in Pathophysiology and Treatment of Schizophrenia)

  • 박소영;한규희
    • 생물정신의학
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    • 제4권2호
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    • pp.162-167
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    • 1997
  • There is no doubt that dopamine plays a critical role in the etiopathogenesis of schizophrenia. However, there appeared some limitations in explaining the complex phenomena of schizophrenia. Recent research data suggest that dysfunction in serotonergic system may be involved. Before the dopamine hypothesis of schizophrenia became established, the interest in serotonin(5-hydroxytryptamine, 5-HT) as an etiological substrate of this illness occurred. Recently the importance and extent of 5-HT's involvement in the pathophysiology and mechanism of action of antipsychotic drug is actively investigated. In recent years, therapeutic success of clozapine and risperidones has increased attention on the interaction between the 5-HT and dopamine systems in schizophrenia. This led to the concept of serotonin-dopamine antagonist for antipsychotics. The authors review the evidence for the role of 5- HT in schizophrenia and serotonin-dopamine interaction.

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Dopamine $D_2$Receptor 효능제인 TNPA의 중추적 항이뇨작용 기전 (Mechanism of Central Antidiuretic Action Induced by TNPA, Dopamine $D_2$Receptor Agonist, in Dogs)

  • 고석태;황명성
    • 약학회지
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    • 제45권4호
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    • pp.397-406
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    • 2001
  • It has been demonstrated previously that R(-)-2,10,11-trihydroxy-N-n-propylnora porphine (TNPA), a dopamine D$_2$receptor agonist, produced the antidiuresis through changes of central friction in dog. This study was investigated about effects of renal denervation and raclopride, a dopamine D$_2$receptor antagonist, on the antidiuresis of TNPA in order to elicidate the mechanism involved in this central antidiuresis induced by TNPA. Antidiresis exhibited by TNPA given into the vein or into carotid artery was not influenced by renal denervation, whereas antidiuresis of TNPA administered into carotid artery was blocked almost perfectly by raclopride pretreated into carotid artery. From these observations it is concluded that central antidiuresis induced by TNPA is brought about through activation of dopamine D$_2$receptor localized in brain, not related to renal nerve activity.

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Effects of Forskolin on Endogenous Dopamine and Acetylcholine Release in Rat Neostriatal Slices

  • Kim, Hwa-Jung
    • Archives of Pharmacal Research
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    • 제19권6호
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    • pp.520-528
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    • 1996
  • The involvement of the cyclic AMP (cAMP) effector system in the release of endogenous dopamine and acetylcholine from the rat neostriatum was assessed. Forskolin, an activator of adenylate cyclase, was used to enhance cAMP production, and the consequence of this enhancement on the spontaneous and potassium stimulated release of dopamine and acetylcholine was evaluated. Neostriatal slices were prepared from Fischer 344 rats and after a preincubation period the release of each endogenous neurotransmitter was measured from the same slice preparation. To measure acetylcholine release the slice acetylcholinesterase (AChE) activity was inhibited with physostigmine, but the release from slices with intact AChE activity was also determined (choline, instead of acetylcholine was detected in the medium). Under both conditions forskolin induced a significant dose-dependent increase in the potassium-evoked release of dopamine. In the same tissue preparations the release of neither acetylcholine (AChE inhibited) nor choline (AChE intact) was affected by forskolin. The results indicate that the CAMP second messenger system might be involved in neuronal mechanisms that enhance neostriatal dopamine release, but stimulation of this second messenger by forskolin does not further enhance neostriatal acetylcholine release.

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Vibrational Analysis of Dopamine Neutral Bae based on Density Functional Force Field

  • 박선경;이남수;이상호
    • Bulletin of the Korean Chemical Society
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    • 제21권10호
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    • pp.1035-1038
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    • 2000
  • Vibrational properties of dopamine neutral species in powder state have been studied by means of the normal mode analysis based on the force constants obtained from the density functional calculation at B3LYP level and the results of Fourier trans form Raman and infrared spectroscopic measurements. Ab initio calculation at MP2 level shows that the trans conformer of dopamine has higher electronic energy about 1.4 kcal/mol than those of the gauche+ and the gauche-conformers, and two gauche conformers have almost the same energies. Free energies calculated at HF and B3LYP levels show very similar values for three conformers within 0.3 kcal/mol. Empirical force field has been constructed from force constants of three conformers, and refined upon ex-perimental Raman spectrum of dopamine to rigorous values. The major species of dopamine neutral base in the powder state is considered a trans conformer as shown in the crystallographic study of dopamine cationic salt.

Limonene Inhibits Methamphetamine-Induced Sensitizations via the Regulation of Dopamine Receptor Supersensitivity

  • Gu, Sun Mi;Kim, Sung Yeon;Lamichhane, Santosh;Hong, Jin Tae;Yun, Jaesuk
    • Biomolecules & Therapeutics
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    • 제27권4호
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    • pp.357-362
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    • 2019
  • Limonene is a cyclic terpene found in citrus essential oils and inhibits methamphetamine- induced locomotor activity. Drug dependence is a severe neuropsychiatric condition that depends in part on changes in neurotransmission and neuroadaptation, induced by exposure to recreational drugs such as morphine and methamphetamine. In this study, we investigated the effects of limonene on the psychological dependence induced by drug abuse. The development of sensitization, dopamine receptor supersensitivity, and conditioned place preferences in rats was measured following administration of limonene (10 or 20 mg/kg) and methamphetamine (1 mg/kg) for 4 days. Limonene inhibits methamphetamine- induced sensitization to locomotor activity. Expression of dopamine receptor supersensitivity induced by apomorphine, a dopamine receptor agonist, was significantly reduced in limonenepretreated rats. However, there was no significant difference in methamphetamine-induced conditioned place preferences between the limonene and control groups. These results suggest that limonene may ameliorate drug addiction-related behaviors by regulating postsynaptic dopamine receptor supersensitivity.

백서(白鼠) 중격측좌핵에서 Haloperidol로 유발된 세포외 도파민 농도 변화에 대한 (-)-3-PPP 전처치 효과 (Effect of Pretreatment of (-)-3-PPP on the Haloperidol-Induced Extracellular Dopamine Concentrations in the Nucleus Accumbens of Rats)

  • 정영철;은홍배;황익근;박태원
    • 생물정신의학
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    • 제8권1호
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    • pp.79-84
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    • 2001
  • Objectives : To investigate the effects of (-)-3-PPP(0.5, 2, and 10mg/kg, s.c.) and haloperidol(0.1, 0.5, and 2mg/kg, s.c.) on the extracellular dopamine concentrations, and the effect of pretreatment with (-)-3-PPP(2mg/kg) on the haloperidol(2mg/kg)-induced extracellular dopamine concentrations in the nucleus accumbens(NAS) of free moving rats. Methods : Dopamine levels in dialysate were determined with high pressure liquid chromatography(HPLC) with electrochemical detection(ECD). Results : (1)(-)-3-PPP had dual actions depending on the doses: at 2mg/kg, it decreased and at 10mg/kg, increased extracellular dopamine concentrations ; (2) haloperidol at all doses increased dopamine levels with higher dose having a greater increase; and (3) pretreatment of (-)-3-PPP reduced the increase in dopamine levels elicited by acute treatment with haloperidol. Conclusions : These findings suggest that pretreatment of (-)-3-PPP in low dose could accelerate the onset of therapeutic effect of haloperidol by diminishing the haloperidol-induced dopamine release in the limbic system.

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Liriodenine이 PC12 세포중의 Dopamine 생합성에 미치는 영향 (Effects of Liriodenine on Dopamine Biosynthesis in PC12 Cells)

  • 김춘매;이재준;윤수옥;김유미;김영균;유시용;이명구
    • 생약학회지
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    • 제34권1호통권132호
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    • pp.55-59
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    • 2003
  • The effects of liriodenine, an aporphine isoquinoline alkaloid, on dopamine content in PCl2 cells were investigated. Treatment of PC12 cells with liriodenine decreased dopamine content in a dose-dependent manner (33.6% inhibition at $10\;{\mu}M$ for 12 h). The $IC_{50}$ in value of liriodenine was $8.4\;{\mu}M$. Dopamine content decreased at 3 h and reached a minimal level at 12 h after the exposure to liriodenine. Under these conditions, the activities of tyrosine hydroxylase and aromatic L-amino acid decarboxylase were also inhibited at $10\;{\mu}M$ of liriodenine by 10.1% and 20.2% relative to control, respectively. In addition, liriodenine inhibited the increase in dopamine content induced by L-DOPA Treatments $(50-100\;{\mu}M)$ in PC12 cells. These results suggest that liriodenine inhibited dopamine biosynthesis and L-DOPA-induced increase in dopamine content by reducing the activities of tyrosine hydroxylase and aromatic L- amino acid decarboxylase in PC12 cells.

쥐의 선조체에 있어서 Physostigmine의 아급성 투여가 Dopamine 대사에 미치는 영향 (Effects of Subacute Administration of Physostigmine on Dopamine Metabolism in Rat Striatum)

  • 임동구;최수형
    • 대한약리학회지
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    • 제28권1호
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    • pp.11-18
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    • 1992
  • Physostigmine을 급성(0.75 mg/kg), 7일간 매일 1회(0.75 mg/kg) 그리고 7일간 연속(0.15 mg/kg/h) 투여한 쥐의 선조체에 있어서 dopamine(DA) 및 대사체와 tyrosine hydroxylase(TH)활성도의 변화를 검색하였다. 급성 투여 1시간 후 선조체의 DA 농도는 변화가 없었으나 dihydroxy-phenylacetic acid(DOPAC)과 homovanillic acid(HVA)농도는 증가하였다. 또한 DA의 turnover의 증가를 제시하는 DOPAC/DA와 HVA/DA의 비율도 증가하였다. 그러나 TH활성도는 24시간 후 감소를 나타내었다. Physostigmine을 매일 및 연속 투여군에서는 DA과 대사체의 농도에는 변화가 없었으나, DA의 turnover의 감소를 제시하는 DA과 대사체의 비율은 감소하였다. 그러나 TH활성도는 매일 투여군에서만 감소를 나타내었다. 이러한 결과는 physostigmine을 급성 및 아급성으로 투여시 dopamine대사의 변화가 있음을 제시한다. 또한 콜린 신경계의 아급성 자극은 dopamine 대사 및 활성도를 감소 시킬 가능성을 시사해 주었다.

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Design, Synthesis, and Functional Evaluation of 1, 5-Disubstituted Tetrazoles as Monoamine Neurotransmitter Reuptake Inhibitors

  • Paudel, Suresh;Wang, Shuji;Kim, Eunae;Kundu, Dooti;Min, Xiao;Shin, Chan Young;Kim, Kyeong-Man
    • Biomolecules & Therapeutics
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    • 제30권2호
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    • pp.191-202
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    • 2022
  • Tetrazoles were designed and synthesized as potential inhibitors of triple monoamine neurotransmitters (dopamine, norepinephrine, serotonin) reuptake based on the functional and docking simulation of compound 6 which were performed in a previous study. The compound structure consisted of a tetrazole-linker (n)-piperidine/piperazine-spacer (m)-phenyl ring, with tetrazole attached to two phenyl rings (R1 and R2). Altering the carbon number in the linker (n) from 3 to 4 and in the spacer (m) from 0 to 1 increased the potency of serotonin reuptake inhibition. Depending on the nature of piperidine/piperazine, the substituents at R1 and R2 exerted various effects in determining their inhibitory effects on monoamine reuptake. Docking study showed that the selectivity of tetrazole for different transporters was determined based on multiple interactions with various residues on transporters, including hydrophobic residues on transmembrane domains 1, 3, 6, and 8. Co-expression of dopamine transporter, which lowers dopamine concentration in the biophase by uptaking dopamine into the cells, inhibited the dopamine-induced endoctytosis of dopamine D2 receptor. When tested for compound 40 and 56, compound 40 which has more potent inhibitory activity on dopamine reuptake more strongly disinhibited the inhibitory activity of dopamine transporter on the endocytosis of dopamine D2 receptor. Overall, we identified candidate inhibitors of triple monoamine neurotransmitter reuptake and provided a theoretical background for identifying such neurotransmitter modifiers for developing novel therapeutic agents of various neuropsychiatric disorders.