IDENTIFICATION AND FUNCTION OF ALPHA-ADRENERGIC RECEPTOR

本研究项目的目的是阐明 α-肾上腺素能儿茶酚胺在影响细胞内 事件 为此，α-肾上腺素能受体的鉴定， 它们在细胞质膜中的生化联系，以及 将研究α-肾上腺素能作用的生理伴随物 详细 由于最近有了 一种非常有用的放射性碘化配体， 可以直接研究，并通过开发适当的细胞 模型 该项目的具体目标是： α-肾上腺素能受体及其在心肌细胞中的调节 膜、培养的原代心肌细胞和某些培养的细胞 线;测试的假设，生化介质的 α-肾上腺素能受体激活直接与 细胞的环AMP复合物，磷脂代谢，或 钙离子;将细胞的药理学反应与占领联系起来 肾上腺素能受体;并进行仔细的 α-肾上腺素能受体的结构-功能结合分析 儿茶酚胺 预计这项研究计划将促进 候选人的发展成为一个独立的调查员，并将建立 这是他已经建立的研究基础。 有几个因素对于实现科学和 提案的个人目标。 其中包括学院的资源 物理学家和外科医生，医学部和申办者作为 以及候选人可以利用的科学专长 在整个研究项目期间。

The objective of this research project is to elucidate the mechanisms of action of the alpha-adrenergic catecholamines in influencing cellular events. To this end, the identification of alpha-adrenergic receptors, their biochemical links in the plasma membrane of the cell, and physiological concomitants of alpha-adrenergic actions will be investigated in detail. The proposal has become feasible by the recent availability of a very useful radioiodinated ligand with which alpha-adrenergic receptors may be studied directly, and by the development of appropriate cellular models. The specific goals of the project are to characterize alpha-adrenergic receptors and to study their regulation in myocardial membranes, cultured primary myocardial cells, and certain cultured cell lines; to test the hypothesis that the biochemical mediators of alpha-adrenergic receptor activation are linked directly to effects upon the cyclic AMP complex of the cell, to phospholipid metabolism, or to the calcium ion; to relate pharmacological responses of; the cell to occupation of alpha-adrenergic receptors; and to conduct a careful structure-function-binding analysis of the alpha-adrenergic catecholamines. It is anticipated that this research plan will foster the candidate's development into an independent investigator and will build effectively upon the research base that she has already established. Several factors will be important in achieving both the scientific and personal goals of the proposal. They include the resources of the College of PHysicians and Surgeons, the Department of Medicine, and the Sponsor as well as the scientific expertise that will be available to the candidate throughout the duration of the research project.