Effects of Dopamine on Pumping ATPase of Rabbit Red Cell Membrane

Chang, We Gon,Ko, Il Sup 慶熙大學校 醫科大學 1990 慶熙 醫大 論文集 Vol.15 No.1

Involvement of D2 Receptor on Dopamine-induced Action in Interstitial Cells of Cajal from Mouse Colonic Intestine

Dong Chuan Zuoa,Pawan Kumar Shahia,Seok Choia,Jae Yeoul Jun,Jong-Seong Park 대한의생명과학회 2012 Biomedical Science Letters Vol.18 No.3

Dopamine is an enteric neurotransmitter that regulates gastrointestinal motility. This study was done to investigate whether dopamine modulates spontaneous pacemaker activity in cultured interstitial cells of Cajal (ICCs) from mouse using whole cell patch clamp technique, RT-PCR and live Ca2+ imaging analysis. ICCs generate pacemaker inward currents at a holding potential of-70 mV and generate pacemaker potentials in current-clamp mode. Dopamine did not change the frequency and amplitude of pacemaker activity in small intestinal ICCs. On the contrary dopamine reduced the frequency and amplitude of pacemaker activity in large intestinal ICCs. RT-PCR analysis revealed that Dopamine2 and 4-receptors are expressed in c-Kit positive ICCs. Dopamine2 and 4 receptor agonists inhibited pacemaker activity in large intestinal ICCs mimicked those of dopamine. Domperidone, dopamine2 receptor antagonist, increased the frequency of pacemaker activity of large intestinal ICCs. In Ca2+-imaging, dopamine inhibited spontaneous intracellular Ca2+ oscillations of ICCs. These results suggest that dopamine can regulate gastrointestinal motility through modulating pacemaker activity of large intestinal ICCs and dopamine effects on ICCs are mediated by dopamine2 receptor and intracellular Ca2+ modulation.

Application of HPLC with Electrochemical Detection to Assaying Tyrosine Hydroxylase Activity and Dopamine Content in Dissociated Cultures of Fetal Rat Brainstem

송동근,위명복,박찬웅,김영희,Song, Dong-Keun,Wie, Myung-Bok,Park, Chan-Woong,Kim, Yung-Hi The Korean Society of Pharmacology 1991 대한약리학잡지 Vol.27 No.1

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. 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.

Antagonists of Both D1 and D2 Mammalian Dopamine Receptors Block the Effects of Dopamine on Helix aspersa Neurons

Kim, Young-Kee,Woodruff, Michael L. Korean Society for Biochemistry and Molecular Biol 1995 Journal of biochemistry and molecular biology Vol.28 No.3

Dopamine mediates inhibitory responses in Helix aspersa neurons from the right parietal lobe ("F-lobe") of the circumoesophageal ganglia. The effects appeared as a dose-dependent hyperpolarization of the plasma membrane and a decrease in the occurrence of spontaneous action potentials. The average hyperpolarization with 5 ${\mu}m$ dopamine was -12 mV (${\pm}1.5$mV, S.D., n=12). Dopamine also modulated the currents 'responsible for shaping the action potentials in these neurons. When dopamine was added and action potentials were triggered by an injection of current, the initial depolarization was slowed, the amplitude and the duration of action potentials were decreased, and the after-hyperpolarization was more pronounced. The amplitude and the duration of action potential were reduced about 15 mV and about 13% by 5 ${\mu}m$ dopamine, respectively. The effects of dopamine on the resting membrane potentials and the action potentials of Helix neurons were dose-dependent in the concentration range 0.1 ${\mu}m$ to 50 ${\mu}m$. In order to show 1) that the effects of dopamine were mediated by dopamine receptors rather than by direct action on ionic channels and 2) which type of dopamine receptor might be responsible for the various effects, we assayed the ability of mammalian dopamine receptor antagonists, SCH-23390 (antagonist of D1 receptor) and spiperone (antagonist of D2 receptor), to block the dopamine-dependent changes. The D1 and D2 antagonists partially inhibited the dopamine-dependent hyperpolarization and the decrease in action potential amplitude. They both completely blocked the decrease in action potential duration and the increase in action potential after-hyperpolarization. The dopamine-induced slowdown of the depolarization in the initial phase of the action potentials was less effected by SCH-23390 and spiperone. From the results we suggest 1) that Helix F-lobe neurons may have a single type of dopamine receptor that binds both SCH-23390 and spiperone and 2) that the dopamine receptor of Helix F-lobe neurons may be homologous with and primitive to the family of mammalian dopamine receptors.

흰쥐 태 뇌간의 세포배양에서 HPLC-전기화학검출을 이용한 Tyrosine Hydroxylase 활성 및 Dopamine의 정량

송동근(Dong-Keun Song),위명복(Myung-Bok Wie),박찬웅(Chan-Woong Park),김영희(Yung-Hi Kim) 대한약리학회 1991 대한약리학잡지 Vol.27 No.1

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. α-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(0.1μM) 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. 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 α-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(0.1μM)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.

Drug-Native Tourette 장애 아동에서 [123I] IPT SPECT로 측정한 기저 신경절 Dopamine Transporter Density 양상

천근아,유영훈 대한신경정신의학회 2002 신경정신의학 Vol.41 No.4

연구목적: 뚜렛 장애가 기저 신경절 presynaptic dopamine 신경계의 기능 이상으로 인한 dopamine 과잉분 포와 연관이 있다는 증거는 많다. 본 연구는 Dopamine transporter density가 dopamine 신경 말단 의 dopamine의 농도와 비례한다는 전제하에 Dopamine transporter density 영상을 보는 I-123- IPT brain SPECT를 이용하여, 약물 비노출(drug-naive) 뚜렛 장애 아동에서 기저 신경절 Dop􀀐 amine transporter density 양상을 알아보고자 하였다. 또한 뚜렛 장애의 틱증상 심각도와 Dopamine transporter density와의 연관성을 알아보고자 하였다. 방 법: 연구대상은 8명의 뚜렛 장애 아동(mean age=9.75±1.98세)과 6명의 정상 대조군(mean age=10.33 ±2.88세)이었다. 8명의 뚜렛 장애 아동 모두 이전에 틱증상 억제 약물을 투여받은 적이 없는 약물- 비노출 상태였다. 뚜렛 장애군과 정상 대조군 모두를 대상으로 I-123 IPT를 정맥주사 후 2시간 후 에 SPECT를 촬영하였으며 그 영상을 분석하여 좌, 우측의 기저 신경절의 특이결합/비특이결합 비율 을 구한 후, 각 군간의 차이를 정량적으로 분석하였다. 뚜렛 장애 아동의 틱증상과 Dopamine tra􀀐 nsporter density와의 연관성을 알아보기 위하여 YGTSS로 측정한 틱증상 총점과 좌, 우측 기저 신 경절 특이결합/비특이결합 비율의 상관관계를 알아보았다. 결 과: 약물 비노출(drug-naive) 뚜렛 장애 아동(n=8)과 정상 아동(n=6)의 좌, 우측의 기저신경절의 특이 결합/비특이결합 비율을 비교해 본 결과 우측 기저 신경절의 특이결합/비특이결합 비율에서는 유의한 차이가 없었다. 그러나 좌측 기저 신경절의 특이결합/비특이결합 비율에서는 약물 비투여 뚜렛 장애 아동군이 정상 아동군보다 유의하게 높은 것으로 나타났다(z=-2.453, p=0.013). 뚜렛 장애 아동의 틱증상 심각도와 좌, 우측 기저 신경절 특이결합/비특이결합 비율과의 상관관계에서는 유의한 연관성 을 보이지 않았다. 결 론: 뚜렛 장애 아동군이 정상 아동군에 비하여 좌측 기저 신경절의 Dopamine transporter density가 유의하게 증가되어 있는 것을 알 수 있었다. 이러한 결과는 뚜렛 장애의 병태생리와 연관된 기저 신 경절 presynaptic dopamine 기능 이상으로 인한 dopamine 과잉 분포에 대한 가설을 지지한다고 볼 수 있다

olanzapin과 Risperidone의 급성 및 만성 투여기가 흰쥐 전전두피질의 Dopamine 농도에 미치는 영향

문선근,정영철,은홍배,황익근,박태원 大韓神經精神醫學會 2002 신경정신의학 Vol.41 No.1

항정신병약물들이 전전두피질의 세포외 dopamine 농도에 미치는 영향은 이 약물들의 음성 증상에 대한 효과와 관련이 있는 것으로 보고 되고 있다. 따라서 본 연구에서는 최근 국내에서 많이 사용되고 있는 olanzapine과 risperidone을 흰쥐에 급성 및 만성 투여를 한 후, 이들 약물들이 전전두피질의 세포외 dopamine 농도에 미치는 영향을 알아보고자 하였다. 샘플은 생체 내 뇌 미세투석법(in vivo brain microdialysis)을 이용하여 얻었고 샘플내 dopamine의 농도는 전기화학적 검출법(electrochemical detection : ECD)을 사용하는 고압액체크로마토그라피(high pressure liquid chromatography : HPLC)로 측정하였다. 그 결과는 다음과 같다. 1) Olanzapine과 risperidone의 급성 투여는 전전두피질 부취의 세포외 dopamine 농도를 증가시켰으며 증가의 정도는 용량 의존적이었다. 2) Olanzapine과 risperidone의 급성 투여에 의해 전전두피질 부위에 나타난 세포외 dopamine 농도의 최고치는 두 약물간에 유의한 차이가 없었다. 3) Olanzapine과 risperidone의 만성 투여는 전전두피질 부위의 세포외 dopamine 농도를 증가시켰으나 그 증가의 정도가 급성 투여에 비해 모두 감소하는 내성 현상이 보였다. 4) Olanzapine과 risperidone의 만성 투여에 의해 전전두피질 부위에 나타나는 세포외 dopamine 농도의 최고치는 olanzapine과 risperidone에 비해 유의하게 높았다. 이상의 결과들은 Olanzapine과 risperidone의 음성 증상에 대한 임상적 효과가 이들 약물이 전전두피질의 세포외 dopamine 농도를 증가시키는 효과와 관견이 있음을 제시한다. Object : It is reported that the effect of antipsychotics on the extracellular dopamine levels in the prefrontal cortex is related to the their effect on the negative symptoms. Therefore, we investigated the acute and chronic effects of olanzapine and risperidone on the extracellular dopamine concentrations in the prefrontal cortex of rat. Samples were obtained using in vivo brain microdialysis. Method : Dopamine levels in the samples were measured by high pressure liquid chromatography with electrochemical detection. Results : 1) Both the acute treatment of olanzapine and risperidone increased the extracellular dopamine concentrations in the prefrontal cortex, dose-dependently. 2) There was a no significant difference in the maximal change of the extracellular dopamine concentrations in the prefrontal cortex induced by the acute treatment of olanzapine and risperidone. 3) Both the chronic treatment of olanzapine and risperidone also increased the extracellular dopamine concentrations in the prefrontal cortex, but they showed the tolerance effect that the degree of increase was smaller than that of the acute treatment. 4) As for the maximal changes of the extracellular dopamine concentrations in the prefrontal cortex induced by the chronic treatment of planzapine and risperidone, the effect of the former was greater than that of the latter. Conclusion : These results suggest that the effects of olanzapine and risperdone on the negative symptoms are related to the increased extracellular dopamine concentrations in the prefrontal cortex induced by these drugs.

Selective Determination of Dopamine with an Amperometric Biosensor Using Electrochemically Pretreated and Activated Carbon/Tyrosinase/Nafion^®-Modified Glassy Carbon Electrode

Rahman, Siti Fauziyah,Min, Kyoungseon,Park, Seok-Hwan,Park, Jae-Hee,Yoo, Jin Cheol,Park, Don-Hee Korean Society for Biotechnology and Bioengineerin 2016 Biotechnology and Bioprocess Engineering Vol.21 No.5

Dopamine, the most important neurotransmitter in the human brain, controls various functions. Dopamine deficiency causes fatal neurological disorders such as Parkinson's disease. Even though various types of electrochemical sensors have been studied to measure dopamine levels, they often have poor selectivity for dopamine due to co-existence of interfering substances (e.g. ascorbic acid). Herein, we aimed to develop a highly sensitive dopamine detection method in the co-existence of ascorbic acid, a major interfering substance in real sample by designing an electrochemically pretreated and activated carbon/tyrosinase/Nafion<TEX>$^{(R)}$</TEX>-modified GCE as an amperometric dopamine biosensor. To maximize the biosensor performance, pH, volume of Nafion<TEX>$^{(R)}$</TEX>, and scan rate were optimized. This electrochemically pretreated and activated carbon/tyrosinase/Nafion<TEX>$^{(R)}$</TEX>-modified GCE could detect as low as <TEX>$50{\mu}M$</TEX> of dopamine with a wide linear range (<TEX>$50{\sim}1,000{\mu}M$</TEX>) within a few seconds. In addition, it had a sensitivity of <TEX>$103mAM/cm^2$</TEX>, which was higher than all previously reported tyrosinase-based dopamine biosensors. In addition, interference effect caused by 4 mM of ascorbic acid was negligible in the co-existence of 1 mM of dopamine. Consequently, this electrochemically pretreated and activated carbon/tyrosinase/Nafion<TEX>$^{(R)}$</TEX>-modified GCE might be applicable as amperometric biosensor for selective detection of dopamine in real samples with interfering substances.

Highly sensitive and selective dopamine detection by an amperometric biosensor based on tyrosinase/MWNT/GCE

Don-Hee Park,Siti Fauziyah Rahman,민경선,박석환,Jae-Hee Park,JIN CHEOL YOO 한국화학공학회 2016 Korean Journal of Chemical Engineering Vol.33 No.12

Dopamine (3,4-dihydroxylphenyl ethylamine) is the most significant neurotransmitter in the human nervous system. Abnormal dopamine levels cause fatal neurological disorders, and thus measuring dopamine level in actual samples is important. Although electrochemical methods have been developed for detecting dopamine with high accuracy, certain substances (e.g., ascorbic acid) in actual samples often interfere with electrochemical dopamine detection. We developed tyrosinase-based dopamine biosensor with high sensitivity and selectivity. An electrochemically pretreated tyrosinase/multi-walled carbon nanotube-modified glassy carbon electrode (tyrosinase/MWNT/GCE) was prepared as an amperometric biosensor for selective dopamine detection. For optimizing the biosensor performance, pH, temperature, and scan rate were investigated. The electrochemically pretreated tyrosinase/MWNT/GCE exhibited not only the highest sensitivity (1,323mAM−1cm−2) compared to previously reported tyrosinase-based dopamine sensors, but also good long-term stability, retaining 90% of initial activity after 30 days. Additionally, ascorbic acid, a major interfering substances, was not oxidized at the potential used to detect dopamine oxidation, and the interfering effect of 4mM ascorbic acid was negligible when monitoring 1mM dopamine. Consequently, the electrochemically pretreated tyrosinase/MWNT/GCE is applicable for highly selective and sensitive dopamine detection in actual samples including interfering substances, thereby extending the practical use to monitor and diagnose neurological disorders.

Human Dopamine Receptor-Conjugated Multidimensional Conducting Polymer Nanofiber Membrane for Dopamine Detection

Park, Seon Joo,Lee, Seung Hwan,Yang, Heehong,Park, Chul Soon,Lee, Chang-Soo,Kwon, Oh Seok,Park, Tai Hyun,Jang, Jyongsik American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.42

<P>In the brain and central nervous system, dopamine plays a crucial role as a neurotransmitter or a local chemical messenger for interneuronal communication. Dopamine is associated with renal, hormonal, and cardiovascular systems. Additionally, dopamine dysfunction is known to cause serious illnesses, such as Parkinson's disease and Alzheimer's disease. Therefore, dopamine detection is essential for medical diagnosis and disease prevention and requires a novel strategy with high sensitivity and selectivity and a rapid response. Herein, we present a novel human dopamine receptor (hDRD1)-conjugated multidimensional conducting polymer nanofiber (NF) membrane for the selective and sensitive detection of dopamine. The membrane, which consists of multidimensional carboxylated poly(3,4-ethylenedioxythiophene) (MCPEDOT) NFs with nanorods, is used as a transistor in a liquid-ion gated field-effect transistor (FET)-based biosensor. Interestingly, hDRD1 is first expressed in Escherichia coli before it is immobilized onto the MCPEDOT NF. The hDRD1 MCPEDOT NF -based FET exhibits a rapid real-time response (<2 s) with high dopamine selectivity and sensitivity performance (approximately 100 84). Furthermore, this FET device can be integrated into a poly(dimethylsiloxane)based microfluidic system and also can retain its high performance in the integrated system, which results in the generation of large-scale dopamine biosensors with a novel geometry.</P>