PHARMACOGENETICS

药物遗传学

• 批准号: 7606512
• 负责人: DANIEL T O'CONNOR
• 金额: $ 0.93万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606512
• 关键词: Blood Circulation; Blood Pressure; Blood Vessels; Blood specimen; Catecholamines; Computer Retrieval of Information on Scientific Projects Database; DNA; Dorsal; Excretory function; Funding; Genes; Genetic Polymorphism; Genomics; Genotype; Grant; Half-Life; Hand; Heart Rate; Human; Individual; Individual Differences; Institution; Mediating; Nerve; Nerve Endings; Neuropeptides; Neurotransmitters; Pharmaceutical Preparations; Pharmacogenetics; Physiology; Preparation; Receptor Signaling; Research; Research Personnel; Resources; Signal Pathway; Source; United States National Institutes of Health; Veins; absorption; base; human subject; neurotransmitter release; receptor; response; vascular bed

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Investigate how neurotransmitters released by sympathetic nerve endings control vascular responses and whether particular genotypes in individuals can predict the response to neurotransmitters. To better understand why individuals differ from one another in their response to neurotransmitters emerging from sympathetic nerve terminals. Humans differ among themselves in their responses to medications. The basis for such inter-individual differences in drug responses is not well understood. In this proposal, we will carefully characterize the responses to neurotransmitters in neurotransmitter-like drugs, representing compounds released from sympathetic nerve endings and impinging upon nerves or blood vessels in the circulation. We will carefully characterize such responses to the neurotransmitters now known to be released from sympathetic nerve endings, including catecholamines and neuropeptides. We characterize these responses in such local vascular beds as the hand (through the dorsal hand vein). In this way, we can isolate drug responses, focusing on those that occur at the receptor or in the downstream signaling pathway and effector responses to the drug. Thus, we eliminate the influence of such systemic factors as absorption, distribution, disposition, excretion and half-life. We also evaluate autonomic responses (blood pressure, heart rate, catecholamines), in human subjects. By obtaining a blood sample for preparation of genomic DNA, and by genotyping individuals at loci likely to influence the drug responses such as the receptor and post-receptor signaling machinery impinged upon by the drug), we will better understand whether particular genes influence drug responses or autonomic physiology (as mediated by receptor polymorphisms) in humans.

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 研究交感神经末梢释放的神经递质如何控制血管反应，以及个体的特定基因型是否可以预测对神经递质的反应。为了更好地理解为什么个体对交感神经末梢产生的神经递质的反应不同。 人类对药物的反应各不相同。药物反应的这种个体间差异的基础尚不清楚。在这项提案中，我们将仔细描述神经递质样药物中神经递质的反应，代表从交感神经末梢释放的化合物，并冲击循环中的神经或血管。我们将仔细 描述了这种对现在已知从交感神经末梢释放的神经递质的反应，包括儿茶酚胺和神经肽。我们的特点，这些反应在这样的局部血管床的手（通过手背静脉）。通过这种方式，我们可以分离药物反应，专注于那些发生在受体或下游信号通路和效应器对药物的反应。因此，我们排除了吸收、分布、处置、排泄和半衰期等全身因素的影响。我们还评估了人类受试者的自主反应（血压，心率，儿茶酚胺）。 通过获得用于制备基因组DNA的血液样本，并通过对可能影响药物反应的基因座（例如药物影响的受体和受体后信号传导机制）的个体进行基因分型，我们将更好地了解特定基因是否影响药物反应或人类的自主生理学（由受体多态性介导）。