BRAIN ANGIOTENSIN RECEPTOR FUNCTION, CONTROL, & ANATOMY

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测脑血管紧张素(Ang II)。 应用匀浆放射性配基结合技术的受体药理学。 这些研究将检验脑血管紧张素Ⅱ受体是否存在于 而不是一个亚型。血管紧张素Ⅱ受体结合亲和力的研究 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著差异，这将表明 存在多种脑血管紧张素II受体亚型。Ang的进一步研究 II受体亚型将使用Ang II类似物来区分亚型 不同的类比有不同的亲和力。这些研究将被延长 研究小鼠脑内离散核中血管紧张素Ⅱ受体部位的药理作用 125I-SAR-1、Ile8-Ang II体外定量脑放射自显影 结合到组织切片上。进一步的研究将调查该物种的存在 可相互转换的高亲和力和低亲和力激动剂结合状态 脑血管紧张素Ⅱ受体。放射性标记血管紧张素Ⅱ拮抗剂的结合 将在不同浓度的Ang II或 三磷酸鸟苷存在和不存在时其激动剂类似物 (GTP)或GTP的稳定类似物。对其他受体系统的类似研究 包括外周组织中的Ang II受体，已经显示出高水平和 受体的低亲和力状态。 第二个特别的目的是研究大脑的功能神经解剖学。 脑血管紧张素Ⅱ受体。这些研究将主要涉及分析 血管紧张素Ⅱ与不同脑区的体外受体结合 放射自显影。老鼠将受到各种治疗，例如， 慢性和急性脑室注射血管紧张素Ⅱ或其 特定脑区的拮抗剂、电解性或化学性损伤， 含有神经元或特定亚细胞的特定神经递质 神经元的元素。根据放射性标记的Ang II的变化 结合不同的大脑区域，这些研究应该导致 脑内含有血管紧张素Ⅱ的神经元成分的特征 感受器，大脑中向大脑区域发送投射的位置 包含Ang II受体的神经递质亚型(例如， 去甲肾上腺素能、多巴胺能)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 血管紧张素能活动是否调节大脑中的Ang II受体。

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.