Activation of Bradykinin B2 Receptor by Kallikrein

激肽释放酶激活缓激肽 B2 受体

• 批准号: 6831683
• 负责人: ERVIN G ERDOS
• 金额: $ 34.75万
• 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 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6831683
• 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）：钾化钾激肽的重要性