MEMBRANE PROCESSING OF BETA-ADRENORECEPTORS

β-肾上腺素受体的膜处理

• 批准号: 3286752
• 负责人: Stephen B Baker
• 金额: $ 7.67万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-05-01 至 1988-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3286752
• 关键词: 6 hydroxydopamine; adenosine triphosphate; adenylate cyclase; corticosteroids; glioma; hyperthyroidism; hypothyroidism; ion transport; membrane permeability; methylation; neoplastic cell; phospholipids; tissue /cell culture

Over the past few years, some major differences between the interaction of agonists and antagonists with the beta-adrenoreceptor have been observed. Agonist binding shows 2 affinity states (high and low) which are determined by the receptor-guanine nucleotide binding protein (N-site) interaction, whereas, antagonist binding shows only a single class of binding sites. The long term objective of the proposed research is to characterize, after irreversible blockade, the process of receptor regeneration, to correlate agonist binding states with biochemical responses and to determine possible cellular components that regulate receptor-N-site interactions. After irreversible blockade of the beta-adrenoreceptor, the time course of recovery will be determined in rat C6-glioma cells with respect to: antagonist binding sites, agonist binding states, cellular localization, receptor down regulation and the stimulation of adenylate cyclase, and phospholipid methylation. The lag period between the recovery of antagonist and agonist high affinity binding sites will be characterized by receptor photoaffinity labeling and attempts will be made to alter the lag period with inhibitors of microtubles, protein synthesis, glycosylation and ATP synthesis. Using whole animals, the regulation of the recovery in the heart and lung antagonist and agonist binding sites, adenylate cyclase stimulation and the lag period between the recovery of antagonist and agonist sites will be determined during hypo- and hyperthyroidism and after treatment with glucocorticoids and 6-hydroxydopamine. The proposed studies will provide basic information on the cellular processing of beta-adrenoreceptors. This information may indicate areas where lesions may occur, resulting in altered receptor coupling and receptor mediated physiological responses associated with disease or drug treatment.

在过去几年中，一些主要的差异之间的相互作用， 已经观察到β-肾上腺素受体的激动剂和拮抗剂。 激动剂结合显示2种亲和力状态（高和低）， 通过受体-鸟嘌呤核苷酸结合蛋白（N-位点）相互作用， 而拮抗剂结合仅显示单一类别的结合位点。 拟议研究的长期目标是表征， 不可逆的阻断，受体再生的过程， 激动剂结合状态与生化反应，并确定可能的 调节受体-N-位点相互作用的细胞组分。 后 β-肾上腺素受体的不可逆阻滞， 将在大鼠C6神经胶质瘤细胞中测定以下方面的回收率： 拮抗剂结合位点，激动剂结合状态，细胞定位， 受体下调和腺苷酸环化酶的刺激，以及 磷脂甲基化 恢复之间的滞后期 拮抗剂和激动剂高亲和力结合位点的特征在于 受体的光亲和标记，并试图改变滞后 微管、蛋白质合成、糖基化和 ATP合成。 使用整个动物，恢复的调节， 心和肺拮抗剂和激动剂结合位点，腺苷酸环化酶 刺激和拮抗剂恢复之间的滞后期 激动剂位点将在甲状腺功能减退和甲状腺功能亢进期间以及 用糖皮质激素和6-羟基多巴胺治疗。 拟议的研究 将提供有关细胞处理的基本信息， β-肾上腺素受体 这些信息可能表明病变的区域 可能发生，导致受体偶联和受体介导的 与疾病或药物治疗相关的生理反应。