RESUMO
UNLABELLED: Excessive or deficient levels of extracellular dopamine have been hypothesized to contribute to a broad spectrum of mood, motor, and thought abnormalities, and dopaminergic system genes have been implicated in aggressive behaviour from animal and human studies. OBJECTIVE. We examined selected members of the dopaminergic system genes for association with child aggression. METHOD: We analyzed polymorphisms in the dopamine transporter DAT1/SLC6A3, dopamine receptor DRD2, and DRD4 genes in our sample of pervasive childhood aggression consisting of 144 cases paired with 144 healthy controls, matched for sex and ethnicity. RESULTS: Aggressive children were significantly more likely to have the at least one copy of the G allele for the DRD2 A-241G polymorphism (genotypic P=0.02; allelic P=0.01). The DRD2 rs1079598 CC genotype was overrepresented in aggressive children compared to controls (genotype P=0.04). The DRD2 TaqIA T allele (P=0.01) and the TT genotype (P=0.01) were also significantly overrepresented in aggressive children. CONCLUSIONS: Our preliminary results suggest that three polymorphisms in DRD2 are associated with childhood aggression. Future studies are required to replicate the current results and to further explore the relationship between the dopamine system and aggressive behaviour in children.
Assuntos
Agressão/fisiologia , Transtornos do Comportamento Infantil/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Dopamina/genética , Predisposição Genética para Doença , Receptores de Dopamina D2/genética , Receptores de Dopamina D4/genética , Canadá , Criança , Feminino , Humanos , Masculino , Polimorfismo GenéticoRESUMO
This article examines the utility of atomic absorption spectroscopy, in conjunction with cold flux assays, to ion channel screening. The multiplicity of ion channels that can be interrogated using cold flux assays and atomic absorption spectroscopy is summarized. The importance of atomic absorption spectroscopy as a screening tool is further elaborated upon by providing examples of the relevance of ion channels to various physiological processes and targeted diseases.
Assuntos
Canais Iônicos/fisiologia , Espectrofotometria Atômica/métodos , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/tendências , HumanosRESUMO
Ion channels have been identified as therapeutic targets in various disorders, such as cardiovascular disease, neurological disease, and cystic fibrosis. Flux assays to detect functional ionic flux through ion channels are becoming increasingly popular as tools for screening compounds. In an optimized flux assay, modulation of ion channel activity may produce readily detectable changes in radiolabeled or nonradiolabeled ionic flux. Technologies based on flux assays are currently available in a fully automated high throughput format for efficient screening. This application offers sensitive, precise, and reproducible measurements giving accurate drug rank orders matching those of patch clamp data. Conveniently, the flux assay is amenable to adaptation for different ion channels, such as potassium, sodium, calcium, and chloride channels, by using suitable tracer ions. The nonradiolabeled rubidium-based flux assay coupled with the ion channel reader (ICR) technology has become very successful in ion channel activity analysis and is emerging as a popular technique in modern drug discovery.
