• 생물정신의학
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• 제8권2호
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• pp.246-250
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• 2001

The dopamine D4 receptor gene has a hypervariable segment in the coding region characterized by a varying number of 48bp repeats in exon III of the gene. Varying the numbers of repeated segments may change the length, structure, and function of the receptor, which makes this gene a possible candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. We evaluated the dopamine D4 receptor genotype in male alcoholics and normal controls. All alcoholics and controls were unrelated and from the Korean population. Genotype and allele frequencies in 67 alcoholics were compared to 67 controls who were free of alcohol abuse, substance abuse, and major mental illness. No association was found between the dopamine D4 receptor allele and alcoholism. This result indicate that there is no association of the dopamine D4 receptor with alcoholism in Korean. Further systemized investigation to determine the role of dopamine D4 receptor gene in alcoholism with a larger sample size will be required.

• Archives of Pharmacal Research
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• 제19권4호
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• pp.275-279
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• 1996

To study the functional roles of dopamine receptors, we decided to raise antibodies against these proteins. To make antigen, we expressed the whole 3rd cytoplasmic loop of dopamine receptors in a fusion protein with glutathione-S-transferase (GST). $For D_2\; and\; D_3$ receptors, it was successful to express and purify fusion proteins for the whole 3rd cytoplasmic loops. However, we could not express the fusion protein for the whole 3rd cytoplasmic loop of $D_4$ dopamine receptor in the bacteria. To study the causes that prevent the bacterial expression of the GST-fusion protein of the 3rd cytoplasmic loop of $D_4$ dopamine receptor, we conducted more detailed studies on $D_4$ dopamine receptor. To locate the region which prevents bacterial expression, we made sequential constructs in the 3rd cytoplasmic loop decreasing the size step by step, and confirmed their expressions in the SDS PAGE. It was found that certain regions of 3rd cytoplasmic loop of $D_4$ dopamine receptor, located in N-terminal side of the 3rd cytoplasmic loop of $D_4$ dopamine receptor suppress the bacterial expression of fusion protein.

• 생물정신의학
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• 제2권1호
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• pp.57-62
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• 1995

항정신병 약물인 clozapine이 주로 작용하는 도파민 수용체로 알려진 도파민 $D_4$ 수용체는 각각 50 염기쌍에 해당하는 크기의 차이가 있음이 알려져 PCR을 이용해 정신분열증 환자와 정상대조군을 대상으로 도파민 $D_4$ 수용체 유전자의 대립형질 분포를 알아보았다. 정신분열증 환자군과 대조군 모두에 있어 여섯종류의 대립형질의 관찰되었으며 정신분열증 환자에서 네번 반복형태의 대립형질이 수적으로 더 많이 관찰되었지만 통계적으로 유의한 차이는 없었으며 정신분열증과 관련된 도파민 $D_4$ 수용체 유전자의 대립형질은 확인되지 않았다. 그러나 보다 객관적인 정보를 얻기 위해서 clozapine에 대한 반응에 따라 정신분열증 환자의 아형을 분류하고 그 아형에 따른 도파민 $D_4$ 수용체 유전자 대립형질분포의 차이에 관한검증이 필요하며, 나아가 도파민 $D_4$ 수용체 유전자의 발현에 있어 정신분열증 환자와 정상인에 차이가 있는지 여부를 밝히는 추적연구가 필요할 것으로 사료된다.

• 생물정신의학
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• 제12권2호
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• pp.107-113
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• 2005

Purpose:In an attempt to predict the interpersonal differences of therapeutic response to antipsychotic drugs on pharmaco-genetic bases, this study was designed to investigate the relationship between the therapeutic response to antipsychotic drugs and Taq I A dopamine $D_2$ receptor polymorphism in schizophrenic patients. Methods:The subjects were 158 patients diagnosed with schizophrenia(DSM-IV). The therapeutic response to antipsychotic drugs was evaluated using the Treatment Response Scale(TRS) retrospectively. Patients were divided into two groups, dopamine receptor antagonist responders, and serotonin-dopamine antagonist responders. The patients' Taq I A dopamine $D_2$ receptor polymorphism was determined by polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP). Results:The dopamine receptor antagonist responders had the A1 allele in significantly higher incidences (${\chi}^2$(1)=4.875, p=0.027, two-tailed). No significant difference was found among the serotonin-dopamine antagonist responders between those with or without the A1 allele. Conclusions:The patients with the A1 allele responded better to dopamine receptor antagonists than those with no A1 allele. Based on these results, it is suggested that the pharmacological effect of dopamine receptor antagonists can be predicted depending on the presence of the A1 allele in schizophrenic patients.

• 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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.89.1-89.1
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• 2003

The signaling pathway of dopamine D$_2$ receptor was studied using yeast two-hybrid system. The 3rd cytoplasmic loop of rat D$_2$ receptor was fond to interact with ALY. The interaction in the yeast was observed only with the 3rd cytoplasmic loop of D$_2$ receptor but not with that of D$_3$ or D$_4$ dopamine receptor. The interaction between two proteins was also confirmed by GST pull-down assay. Co-expression of D$_2$ receptor and ALY enhanced the expression of Lef-1 promoter in C6 cells and the promoter of D$_2$ dopamine receptor itself.

• Biomolecules & Therapeutics
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• 제10권1호
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• pp.50-58
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• 2002

lt had been reproted previously that (${\pm}$)6-chloro-7,8-dihydroxy-1-phenyl 2,3,4,5-tetra-hydro -lH-3benzazepine (SKF 81297), dopamine $D_1$ receptor agonist, produced diuresis by both Indirect action through central function and direct action being induced in kidney. This study was attempted in order to examine the diuresis mechanism of such SKF 81297 Diuretic action of SKF 81297 given into the vein or the carotid artery was not affected by renal denervation, whereas diuretic action of SKF 81297 administered into a renal artery was blocked completely by renal denervation, and then diuretic action of SKF 81297 injected into carotid artery was inhibited by SCH 23390, dopamine $D_1$ receptor antagonist, given into carotid artery. Above results suggest that indirect diuretic action of SKF 81297 elicites through central dopamine $D_1$ receptor and direct diuresis in kidney by influence of renal nerves.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.270.1-270.1
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• 2002

The signaling pathway of D2 dopamine receptor was studied using yeaslt two-hybrid system.. The 3rd cytoplasmic loop of rat D2 dopamine receptor was used to screen the cDNA library of mouse brain. and ALY was found to interact with it. The interaction in the yeast was observed only with the 3rd cytoplasmic loop of D2 dopamine receptor but not with that of D3 or D4 dopamine receptor. The interaction between two proteins was also confirmed by GST pull-down assay. (omitted)

• 생물정신의학
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• 제4권2호
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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.

• Biomolecules & Therapeutics
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• 제2권1호
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• pp.16-22
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• 1994

Using 2 to 4 day-old postnatal rats, primary brain cell cultures were made from various brain regions (substantia nigra, hippocampus, striatum, and nucleus accumbens). Whole-cell patch clamp technique was used for electrophysiological studies. Neurons cultured from substantia nigra were characterized more in detail to test whether these cultured neurons were appropriate for physiological studies. Immunocytochemical and electrophysiological properties of these cultured neurons agreed with those from other in vivo or in vitro studies suggesting that cultured neurons maintained normal cytological and physiological conditions. Modulation of ionic channels through dopamine receptors were studied from brain areas where dopamine plays important roles on brain functions. When neurons were clamped near resting membrane potential (-74mV), R(+), R(+)-SKF 38393, a specific D$_1$receptor agonist, activated cultured striatal neurons, and dopamine itself produced biphasic responses. Responses of cultured hippocampal neurons to dopamine agonists were kinds of mirror images to those from striatal neurons; D$_1$receptor agonists inhibited hippocampal neurons but quinpirole, a D$_2$receptor agonist, activated them. Neurons cultured from nucleus accumbens were inhibited by dopamine.