BRAIN ANGIOTENSIN RECEPTOR FUNCTION, CONTROL, & ANATOMY

脑血管紧张素受体功能、控制、

• 批准号: 3402284
• 负责人: Robert Charles Speth
• 金额: $ 8.89万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3402284
• 关键词: angiotensin II; angiotensins; autoradiography; blood brain barrier; brain mapping; brain metabolism; dorsal motor nucleus; experimental brain lesion; hormone inhibitor; mathematical model; neuroanatomy; neurochemistry; neuropharmacology; neurotoxins; neurotransmitters; radiotracer; solitary tract nucleus

The long-term objective is to characterize angiotensinergic activity in the CNS. The first specific aim is to examine the brain angiotensin (Ang II) receptor pharmacology using homogenate radioligand binding techniques. These studies will examine whether brain Ang II receptors exist in more than one subtype. The binding affinity of Ang II receptor sites for 125I-Sar-1,Ile8-Ang II in different brain areas will be determined. If significant differences in binding affinity are observed, this will suggest that multiple brain Ang II receptor subtypes exist. Further studies of Ang II receptor subtypes will use Ang II analogs to discriminate subtypes with different affinities for different analogs. These studies will be extended to examine the Ang II receptor site pharmacology in discrete nuclei of the brain using quantitative in vitro autoradiography of 125I-Sar-1,Ile8-Ang II binding to tissue sections. Further studies will investigate the existence of interconvertible high and low affinity agonist binding states of the brain Ang II receptor. The binding of a radiolabeled antagonist of Ang II will be carried out in the presence of varying concentrations of Ang II or its agonist analogs in the presence and absence of guanosine triphosphate (GTP) or a stable analog of GTP. Similar studies of other receptor systems including Ang II receptors in peripheral tissues have demonstrated high and low affinity states of the receptors. The second specific aim is to examine the functional neuroanatomy of the brain Ang II receptor. These studies will primarily involve analysis of Ang II binding in discrete brain regions using in vitro receptor autoradiography. Rats will be subjected to various treatments, e.g., chronic and acute intraventricular administration of Ang II or its antagonist, electrolytic or chemical lesions of specific brain areas, specific neurotransmitter containing neurons or specific subcellular elements of neurons. Based upon the alterations in radiolabeled Ang II binding to various brain regions, these studies should lead to a characterization of the neuronal elements in the brain which contain Ang II receptors, the sites in the brain which send projections to brain areas containing Ang II receptors, the neurotransmitter subtype (e.g., noradrenergic, dopaminergic) of neurons containing And II receptors, the neurotransmitter and/or neurohormonal role of Ang II in the brain, and whether angiotensinergic activity regulates Ang II receptors in the brain.

长期目标是表征血管紧张素能活性 中枢神经系统。 第一个具体目标是检查大脑血管紧张素（Ang II） 使用匀浆放射性配体结合技术的受体药理学。 这些研究将检验大脑中的 Ang II 受体是否存在于更多的细胞中。 多于一种亚型。 Ang II 受体位点的结合亲和力 测定不同脑区的125I-Sar-1、Ile8-Ang II。 如果 观察到结合亲和力的显着差异，这表明 存在多种大脑 Ang II 受体亚型。 昂的进一步研究 II 受体亚型将使用 Ang II 类似物来区分亚型 不同类似物有不同的亲和力。 这些研究将被扩展 检查血管紧张素II受体位点药理学在离散细胞核 使用 125I-Sar-1、Ile8-Ang II 的体外定量放射自显影技术对大脑进行检测 与组织切片结合。 进一步的研究将调查是否存在 的可相互转换的高和低亲和力激动剂结合状态 脑血管紧张素II受体。 Ang II 放射性标记拮抗剂的结合 将在不同浓度的 Ang II 或 存在和不存在三磷酸鸟苷时其激动剂类似物 (GTP) 或 GTP 的稳定类似物。 其他受体系统的类似研究 包括外周组织中的 Ang II 受体已被证明具有高和 受体的低亲和力状态。 第二个具体目标是检查神经功能解剖学 脑血管紧张素II受体。 这些研究将主要涉及分析 使用体外受体在离散大脑区域中结合 Ang II 放射自显影。 大鼠将接受各种治疗，例如 慢性和急性心室内给予Ang II或其 特定大脑区域的拮抗剂、电解或化学损伤， 含有神经元或特定亚细胞的特定神经递质 神经元的元素。 基于放射性标记的 Ang II 的改变 与不同的大脑区域结合，这些研究应该导致 大脑中含有 Ang II 的神经元元件的表征 受体，大脑中向大脑区域发送投射的部位 含有血管紧张素II受体，神经递质亚型（例如， 去甲肾上腺素能、多巴胺能）的神经元含有 和 II 受体， Ang II 在大脑中的神经递质和/或神经激素作用，以及 血管紧张素能活性是否调节大脑中的 Ang II 受体。