Activation of Bradykinin B2 Receptor by Kallikrein

激肽释放酶激活缓激肽 B2 受体

• 批准号: 6620283
• 负责人: ERVIN G ERDOS
• 金额: $ 34.25万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6620283
• 关键词: ACE inhibitors; arachidonate; bradykinin; calcium flux; cytoprotection; kallikreins; neuropeptide receptor; receptor expression; recombinant proteins; renin angiotensin system; serine proteinases; thrombin receptor; tissue /cell culture; transfection

DESCRIPTION (provided by applicant): The importance of the kallikrein-kinin system in regulating cardiovascular function in health and disease is well established. Bradykinin (BK) and its congener, Lys-BK, are released by kallikreins from plasma kininogens. Many successful therapeutic applications of the angiotensin I converting enzyme (ACE; kininase H) inhibitors are attributed to augmenting the effects of BK on its 7-transmembrane-spanning B2 receptor. The aim of this application is to show that besides the peptide ligands, the BK B2 receptor is also directly activated by kallikreins and some other serine proteases. We demonstrated in our initial studies that human kallikrein activated the B2 receptor in nM concentrations without kinin release and this is abolished by specific receptor blocker. In expanding the exploratory experiments, according to Specific Aims 1 and 2, we will use recombinant human kallikrein to activate the human B2 receptor, expressed in transfected cells and in endothelial cells that constitutively express the native receptor. Receptor activation will be assessed by measuring arachidonic acid release,

描述（由申请人提供）：激肽释放酶-激肽的重要性 健康和疾病中调节心血管功能的系统良好 已确立的。缓激肽 (BK) 及其同类物 Lys-BK 由 来自血浆激肽原的激肽释放酶。许多成功的治疗应用 血管紧张素 I 转换酶 (ACE；激肽酶 H) 抑制剂 增强 BK 对其 7 次跨膜 B2 受体的影响。 本申请的目的是证明除了肽配体之外，BK B2 受体也可直接被激肽释放酶和其他一些丝氨酸激活 蛋白酶。我们在初步研究中证明，人类激肽释放酶 以 nM 浓度激活 B2 受体而不释放激肽，这 被特异性受体阻滞剂消除。在拓展探索的过程中 实验中，根据具体目标1和2，我们将使用重组人 激肽释放酶激活在转染细胞中表达的人类 B2 受体 以及组成型表达天然受体的内皮细胞。 受体激活将通过测量花生四烯酸释放来评估，