PHARMACOGENETICS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 研究交感神经末梢释放的神经递质如何控制血管反应，以及个体中特定的基因类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。药物反应的个体间差异的基础还不是很清楚。在这项提案中，我们将仔细描述神经递质类药物对神经递质的反应，这些药物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。我们会小心地 描述这种对目前已知的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。我们在手部(通过手背静脉)这样的局部血管床上描述了这些反应。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药物效应反应中的反应。因此，我们消除了吸收、分布、处置、排泄和半衰期等系统性因素的影响。我们还评估了受试者的自主神经反应(血压、心率、儿茶酚胺)。通过获取血液样本以制备基因组DNA，以及对可能影响药物反应的基因座(如药物影响的受体和受体后信号机制)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人类的药物反应或自主生理(由受体基因多态介导)。

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.