The regulation of dilated cardiomyopathy by dopamine D5 receptor through inhibiting oxidative stress / 中国比较医学杂志

Objective To determine whether dopamine D5 receptor (D5R) regulates the development of dilated cardiomyopathy (DCM) by inhibiting oxidative stress.Methods We developed heart-specific hD5 mutant (α-MHC-hD5F173L) and wild type (α-MHC-hD5WT) transgenic mice.The NOX2 expression and ROS production were tested in the transgenic mice at three month of age.The α-MHC-hD5F173L mice were treated with either NADPH oxidase inhibitor Apocynin (1mmol/kg/day) or phosphate-buffered saline (PBS) as control by intraperitoneal injection for 4 weeks.After then, the indexes of heart function were measured.The hD5WT and hD5F173L were transfected respectively in rat H9C2 cells, in which ROS production and NOX2 expression were detected at basal level.Results The ROS production and NOX2 expression were higher in the heart of α-MHC-hD5F173L than α-MHC-hD5WT mice.Apocynin treatment improved the heart function of α-MHC-hD5F173L mice.NOX2 expression and ROS production were higher in hD5F173L than hD5WT transfected H9C2 cells.Conclusions Dopomine D5 receptor may prevent DCM development by inhibiting oxidative stress.

Effect of Insulin on D_5 Dopamine Receptor Expression and Function in Renal Proximal Tubule Cells / 中华高血压杂志

Objective To investigate the effect of insulin on D_5 dopamine receptor expression and function in renal proximal tubule (RPT).Methods Immortalized RPT cells and D_5 receptor transfected HEK293 (HEK-D_5) cells were used in the study to investigate the effect of insulin on D_5 receptor expression and function,and those effects were compared in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The function of D_5 receptor was determined by measurement of the Na~+-K~+-ATPase activity in HEK-D_5 cells. Results Insulin increased D_5 receptor protein expression in a concentration and time-dependent manner in WKY RPT cells,but not in SHR.The basal level of D_5 receptor expression was higher in WKY cells than that in SHR cells. Stimulation with fenoldopam(D_1-like dopamine receptor agonist) inhibited the Na~+-K~+-ATPase activity;pretreat- ment with insulin increased the inhibitory effect of fenoldopam on Na~+-K~+-ATPase activity in HEK-D_5 cells. Conclusion The abnormal regulation of insulin on D_5 receptor expression and function might be involved in the path- ogenesis of essential hypertension.

A Family-based and Case-control Association Study of the Dopamine D5 Receptor Gene Polymorphism in Attention Deficit Hyperactivity Disorder / 신경정신의학

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.

A Family-based and Case-control Association Study of the Dopamine D5 Receptor Gene Polymorphism in Attention Deficit Hyperactivity Disorder / 신경정신의학

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.

The Association between the Dopamine D5 Receptor Genotype and Treatment Response for Korean Schizophrenic Patients

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.

An Association Study between the Dopamine D5 Receptor Gene and Korean Schizophrenia / 신경정신의학

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.

Association Study of the Sequence Mutation(T978C) of the Dopamine D5 Receptor Gene in Korean Schizophrenics / 신경정신의학

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.