Activation of Bradykinin B2 Receptor by Kallikrein

描述（由申请人提供）：激肽释放酶-激肽的重要性 系统在调节心血管功能的健康和疾病是很好的 确立了习缓激肽（BK）及其同源物Lys-BK由 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转化酶（ACE;激肽酶H）抑制剂被认为是 增强BK对其7-跨膜B2受体的作用。 本申请的目的是表明，除了肽配体，BK B2受体也直接被激肽释放酶和一些其他丝氨酸激活。 蛋白酶我们在最初的研究中证明， 在nM浓度下激活B2受体而不释放激肽， 被特异性受体阻断剂所消除。在扩大探索性的 根据特定目的1和2，我们将使用重组人 激肽释放酶激活人B2受体，在转染细胞中表达 以及在组成型表达天然受体的内皮细胞中。 通过测量花生四烯酸释放来评估受体活化，

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,