BACKGROUND: Dopamine receptors are strong candidates for involvement in schizophrenia and are target of a wide variety of antipsychotics. Dopamine D5 receptor(DRD5) gene polymorphisms may be associated with various treatment response. The purpose of our study was define to what significance can be held as a predictor of treatment response in this polymorphism. METHOD: The total number of 116 Korean chronic schizophrenic patients was assessed after 48 weeks treatment. The Positive and Negative Syndrome Scale(PANSS) was rated for the clinical response to various antipsychotics. With the use of polymerase chain reaction amplification, we assessed this dopamine D5 receptor polymorphism in schizophrenic patients who had been treated with antipsychotics, and related genotype with treatment response, to test the hypothesis that DRD5 polymorphism may lead to varying resonse to antipsychotic. RESULT: DRD5 polymorphism was not associated with treatment response to a variety of antipsychotics in chronic schizophrenic patients. CONCLUSION: Genetic variation of D5 receptors do not predict treatment response to antispychotics.
Antipsychotic Agents ; Dopamine* ; Genetic Variation ; Genotype* ; Humans ; Polymerase Chain Reaction ; Receptors, Dopamine ; Receptors, Dopamine D5* ; Schizophrenia

OBJECTIVE: This study was performed to assess the possible involvement of the dopamine D5 receptor gene(DRD5) in the etiology of schizophrenia. METHODS: We identified the distribution of the T978C varient of the dopamine D5 receptor gene in 100 schizophrenics and 100 normal controls in Korean population, and evaluated the association between two groups. RESULTS: There were no significant differences in genotype frequency of T978C variation and genotype prevalence of homozygotes between schizophrenic and control groups. There was no significant difference in T978C allele frequencies between schizophrenic and control groups. CONCLUSION: We present evidence of a lack of allelic association between the exonic common polymorphism of the dopamine D5 receptor gene and Korean schizophrenic patients. The assumption that the T978C varient of the dopamine D5 receptor gene has a genetic role in the development of schizophrenia was not examined by this case-control study. However, because it is considered that DRD5 may act as the expression factor for the symptoms of schizophrenia or affect the difference in an individual's susceptibility to the disease, future studies to investigate the influence of other variations of DRD5 are needed.
Case-Control Studies ; Dopamine* ; Exons ; Gene Frequency ; Genotype ; Homozygote ; Humans ; Prevalence ; Receptors, Dopamine D5* ; Schizophrenia

OBJECTIVE: This study was performed to define the genetic relationship between the micro-satellite (CT/GT/GA)n polymorphism for the dopamine D5 receptor gene and schizophrenia. An association study in 100 schizophrenic patients and 100 normal controls of Korea was made by means of using polymerase chain reaction. RESULTS: The microsatellite(D5(CT/GT/GA)n) had 11 alleles. There was a significant difference in the allele distribution between schizophrenia and normal controls(p<0.05). In schizophrenic patients, the frequency of allele A10 was decreased. As to the genotype distribution, there was no difference in both groups. CONCLUSIONS: This finding suggests that dopamine D5 gene is likely to be related to the development of schizophrenia in Korea but with only this result, we cannot come to the conclusion that this genetic locus is the genetic determinant of schizophrenia. Further studies of dopamine D5 receptor genetic locus that can confirm this result should be made.
Alleles ; Dopamine* ; Genetic Loci ; Genotype ; Humans ; Korea ; Polymerase Chain Reaction ; Receptors, Dopamine D5* ; Schizophrenia*

OBJECTIVES: Recent genetic studies have suggested a preferential transmission of the Dopamine D5 receptor gene (DRD5) 148bp marker allele. The aim of this study is to test the association between DRD5 and ADHD. METHODS: 106 Korean children with ADHD and their parents were analyzed using the transmission disequilibrium test (TDT) and haplotype-based haplotype relative risk test (HHRR). And also the ADHD children were compared with 212 age and gender matched normal controls. RESULTS: We found the evidence for an association of short alleles of DRD5 dinucleotide repeat polymorphism in both case control and family based studyies. Additionally, we observed some evidence for biased transmission of allele 152 bp and 144 bp. CONCLUSION: Our results lend credence to the notion that the relationship between ADHD and DRD5 is complex. The number of cases and informative transmissions in our study were small, therefore it would be premature to make any conclusions concerning the role of DRD5 in ADHD. Further work is needed to support these findings.
Alleles ; Attention Deficit Disorder with Hyperactivity* ; Bias (Epidemiology) ; Case-Control Studies* ; Child ; Dinucleotide Repeats ; Dopamine* ; Haplotypes ; Humans ; Parents ; Receptors, Dopamine D5*

OBJECTIVES: Recent genetic studies have suggested a preferential transmission of the Dopamine D5 receptor gene (DRD5) 148bp marker allele. The aim of this study is to test the association between DRD5 and ADHD. METHODS: 106 Korean children with ADHD and their parents were analyzed using the transmission disequilibrium test (TDT) and haplotype-based haplotype relative risk test (HHRR). And also the ADHD children were compared with 212 age and gender matched normal controls. RESULTS: We found the evidence for an association of short alleles of DRD5 dinucleotide repeat polymorphism in both case control and family based studyies. Additionally, we observed some evidence for biased transmission of allele 152 bp and 144 bp. CONCLUSION: Our results lend credence to the notion that the relationship between ADHD and DRD5 is complex. The number of cases and informative transmissions in our study were small, therefore it would be premature to make any conclusions concerning the role of DRD5 in ADHD. Further work is needed to support these findings.
Alleles ; Attention Deficit Disorder with Hyperactivity* ; Bias (Epidemiology) ; Case-Control Studies* ; Child ; Dinucleotide Repeats ; Dopamine* ; Haplotypes ; Humans ; Parents ; Receptors, Dopamine D5*

OBJECTIVEAttention deficit hyperactivity disorder (ADHD) is one of the most common behavior disorders in childhood and adolescent. The etiology of ADHD is unknown. The aim of this study was to investigate the relationship between each of the 14 polymorphisms in the five candidate genes and ADHD, and between the combination of some polymorphisms in those genes and ADHD, in attempting to examine whether combinations of genotypes would confer a significant susceptibility to ADHD.

METHODSOne hundred and thirty-nine children with ADHD and one hundred and nineteen normal children were enrolled. Eight single nucleotide polymorphisms (SNP) of three candidate genes were examined with PCR and RFLP techniques. 48 bp VNTR in DRD4 gene was examined with PCR, nondenaturing polyacrylamide gel electrophoresis and silver staining. Five microsatellites (MS) of three candidate genes were examined with genotyping. The relationship between the combinations of 12 polymorphisms and ADHD was examined with logistic regression analysis.

RESULTS1.The frequency of 1065T/1065T genotype and the 1065T allele were significantly higher in ADHD children than that in normal controls (P<0.05). The frequency of -48G/-48G genotype of the A-48G polymorphism of DRD1 gene was significantly lower in ADHD children than that in normal controls (P<0.05). 2. A specific combination of three polymorphisms in the two genes showing an association with ADHD gave a prediction level of 77.5%.

CONCLUSIONSThe T1065G polymorphism in the SNAP-25 may be associated with ADHD. The 1065T/1065T genotype and the 1065T allele may be a risk factor for ADHD. The A-48G polymorphism of DRDI may be associated with ADHD. The -48G/-48G genotype may be a protective factor for ADHD. The specific combination of three sites of SNP in SNAP-25 gene and DRDI gene is found and shows an association with ADHD in 12 polymorphisms of the five candidate genes on glutamatergic/dopaminergic pathway.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; genetics ; Child ; Female ; Humans ; Logistic Models ; Male ; Minisatellite Repeats ; Polymorphism, Single Nucleotide ; Receptors, Dopamine D3 ; genetics ; Receptors, Dopamine D4 ; genetics ; Receptors, Dopamine D5 ; genetics ; Receptors, N-Methyl-D-Aspartate ; genetics ; Synaptosomal-Associated Protein 25 ; genetics

D5 receptor is a subtype of dopamine D1-like receptor, and it plays a functional role in many neurological disorders. Some natural compounds from Chinese herbs, which were shown to have the property as that of receptor agonist, might provide a rich source in search of new candidates for therapeutic use. For exploring this possibility, we developed a cell-based high throughput (HTS) D5 receptor assay to screen the herb-based natural compound library established in our centre. The D5 receptor plasmid (hD5R/pcDNA3.1) and reporter gene plasmid (4 x CRE/TK/Luci/pGL3) were co-transfected into HEK293 cell line. After G418 being selected, the monoclonal cell lines bearing hD5R and the reporter gene were established and used for agonist screening. To optimize the assay condition, the effects of some factors such as cell number per well, incubation time, and the doses of SKF38393 (a potent selective partial D1-like agonist) were examined by using forskolin, a positive compound for cAMP response element. The best condition for this HTS assay included: the cell number at 5 x 10(4)/mL, the dose of forskolin at 5-20 micromol/L, the dose of SKF38393 at 100 nmol/L-100 micromol/L, and the agonist incubation time at 6 -8 h. Thereafter, water extracts from more than 200 Chinese herbs in our library were screened and three of these water extracts showed positive activity, with higher or similar activity as SKF38393. In conclusion, we have established a cell-based HTS assay for D5 receptor agonist screening, and by use of this HTS assay, 3 Chinese herbs maybe contain components exhibiting D5 receptor agonist property. This work provides an alternative vision of how to use herb medicines and a way to develop potential drugs for treatment of neurological disorders.
Cell Line ; Dopamine Agonists ; isolation & purification ; Drug Evaluation, Preclinical ; methods ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; High-Throughput Screening Assays ; methods ; Humans ; Plants, Medicinal ; chemistry ; Receptors, Dopamine D5 ; agonists

OBJECTIVE: To reveal the genetic polymorphisms of four SNP loci (rs77434921, rs2076907, rs6283, rs1800762) in D5 gene of dopamine receptor (DRD5) in Northern Chinese Han population. METHODS: Four SNP loci of the DRD5 gene of 206 unrelated individuals in Northern Chinese Han population were separately amplified and sequenced by PCR technique and statistically analyzed by Haploview v4.1 software. RESULTS: In Northern Chinese Han population, the genotype frequency distribution of rs77434921, rs2076907, rs6283 and rs1800762 loci in the DRD5 gene were all in accordance with Hardy-Weinberg equilibrium. DP value was 0.145, 0.532, 0.602 and 0.159, while PE value was 0.004, 0.079, 0.196 and 0.007. A linkage disequilibrium among these four SNP loci was also demonstrated, which might infer five haplotypes. CONCLUSION rs2076907 and rs6283 loci of DRD5 gene in the Northern Chinese Han population have high genetic polymorphisms, which can be useful for forensic identification of individuals.
Asian People/genetics* ; China/ethnology* ; DNA Primers/genetics* ; Forensic Genetics ; Gene Frequency ; Genetic Markers ; Genotype ; Haplotypes ; Humans ; Linkage Disequilibrium ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Receptors, Dopamine D5/genetics*

OBJECTIVETo explore the possible differential trafficking properties of the dopamine D1-like receptor subtypes, D1 receptor and D5 receptor.

METHODSTo visualize distributions of dopamine D1-like receptor subtypes at subcellular level, the yellow and cyan variants of green fluorescent protein (GFP) were used to tag D1 and D5 receptors. After transfection with the tagged dopamine receptors, the neuroblastoma cells NG108-15 were treated with D1 agonist SKF38393 or acetylcholine (ACh). Then we observed the subcellular distributions of the tagged receptors under the confocal microscopy and tried to determine trafficking properties by comparing their distribution patterns before and after the drug treatment.

RESULTSIn resting conditions, D1 receptors located in the plasma membrane of NG108-15 cells, while D5 receptors located in both plasma membrane and cytosol. With the pre-treatment of SKF38393, the subcellular distribution of D1 receptors was changed. The yellow particle-like fluorescence of tagged D1 receptors appeared in the cytosol, indicating that D1 receptors were internalized into cytosol from the cell surface. Same situation also occurred in ACh pre-treatment. In contrast, the subcellular distribution of D5 receptors was not changed after SKF38393 or ACh treatment, indicating that D5R was not translocated to cell surface. Interestingly, when D1 and D5 receptors were co-expressed in the same cell, both kept their distinct subcellular distribution patterns and the trafficking properties.

CONCLUSIONOur present study reveals that in NG108-15 nerve cells, dopamine D1 and D5 receptors exhibit differential subcellular distribution patterns, and only D1 receptor has a marked trafficking response to the drug stimulation. We further discuss the potential role of the differential trafficking properties of D1-like receptors in complex modulation of DA signaling.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; pharmacology ; Acetylcholine ; pharmacology ; Animals ; Cell Line ; Dopamine Agonists ; pharmacology ; HeLa Cells ; Humans ; Luminescent Proteins ; genetics ; Mice ; Microscopy, Confocal ; methods ; Neuroblastoma ; Protein Transport ; drug effects ; Rats ; Receptors, Dopamine D1 ; metabolism ; Receptors, Dopamine D5 ; metabolism ; Subcellular Fractions ; metabolism ; ultrastructure ; Transfection ; methods