KININS IN THE REGULATION OF VASCULAR FUNCTION

激肽对血管功能的调节

• 批准号: 6349167
• 负责人: A G SCICLI
• 金额: $ 19.21万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6349167
• 关键词: Xenopus oocyte; angiotensins; blood pressure; bradykinin; cell growth regulation; enzyme inhibitors; fibrinolysis; gene expression; hormone receptor; hormone regulation /control mechanism; laboratory rat; neuropeptide receptor; nitric oxide synthase; renin angiotensin system; tissue /cell culture; vascular endothelium; vasodilatation

We have recently discovered a new protein which exhibits potent vasoconstrictor activity when applied to isolated vascular rings. We demonstrated that it is an enzyme belonging to the kallikrein family of serine proteases. The gene for this protein has been identified and the nucleotide sequence of its mRNA is available. We named the substance submandibular enzymatic vasoconstrictor (SEV) because it was isolated from the rat submandibular gland and requires enzymatic activity to contract arterial rings. We found that the mRNA for SEV is present in arteries, cultured vascular smooth muscle cells and kidney. When injected into rats, SEV caused a marked increase in blood pressure. We propose to test the general hypothesis that SEV participates in the regulation of vascular resistance and renal function. Furthermore, an unknown member of the kallikrein family is present in the vascular pole of the glomerulus, where it may play a role in the regulation of glomerular function. To further our understanding of the physio pathological role of these new kallikrein- related enzymes, we propose: I): to localize SEV and its mRNA in tissue using the polymerase chain reaction, in situ hybridization, immunohistochemistry and RIA. In addition, we will determine whether vascular tissue contains binding sites for SEV and whether SEV releases a vasoconstrictor peptide(s); II): to determine: a) whether SEV is released as an endocrine and/or exocrine hormone. We will study release of SEV into the salivary and urinary compartments of the submandibular gland and kidney, and in the venous effluent of these organs, respectively, b) the factor(s) that regulate tissue concentration and release of SEV and mRNA levels. III): to determine the effects of acute administration of SEV on blood pressure, cardiac output and renal function, and whether blockade of endogenous SEV with Fab fragments of monoclonal antibodies alters any of these parameters. IV): To identify, purify and characterize the kallikrein-related protein expressed in the vascular pole of the glomerulus.

我们最近发现了一种新的蛋白质， 血管收缩活性时，适用于孤立的血管环。 我们 证明它是一种属于激肽释放酶家族的酶， 丝氨酸蛋白酶 这种蛋白质的基因已经被鉴定出来， 其mRNA的核苷酸序列是可用的。 我们将这种物质命名为 下颌下酶促血管收缩剂（SEV），因为它是从 大鼠下颌下腺，需要酶活性收缩 动脉环 我们发现SEV的mRNA存在于动脉中， 培养的血管平滑肌细胞和肾脏。 当注射到大鼠体内时， SEV导致血压显著升高。 我们建议测试 SEV参与血管调节的一般假设 阻力和肾功能。 此外，一名不知名的 激肽释放酶家族存在于肾小球的血管极，其中 它可能在肾小球功能的调节中起作用。 进一步 我们对这些新的激肽释放酶的生理病理作用的理解， 相关酶，我们建议：I）：定位SEV及其mRNA在组织中 使用聚合酶链反应，原位杂交， 免疫组化和RIA。 此外，我们将确定是否 血管组织含有SEV的结合位点，以及SEV是否释放一种 血管收缩肽; II）：确定：a）SEV是否释放 作为内分泌和/或外分泌激素。 我们将研究将SEV释放到 下颌下腺的唾液和尿液隔室， 肾，和这些器官的静脉流出物中，分别，B） 调节组织浓度和SEV和mRNA释放的因子 程度. III）：确定SEV急性给药对 血压、心输出量和肾功能，以及是否阻断 内源性SEV与单克隆抗体的Fab片段改变了任何 这些参数。 四）：鉴定、纯化和表征 激肽释放酶相关蛋白在血管极表达， 肾小球