KININS IN THE REGULATION OF VASCULAR FUNCTION

我们最近发现了一种新的蛋白质，它显示出 当应用于分离的血管环时具有血管收缩活性。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，并且 获得了ITS基因的核苷酸序列。我们把这种物质命名为 颌下酶性血管收缩因子(SEV)，因为它是从 大鼠下颌下腺，需要酶活性才能收缩 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。当注射到老鼠体内时， SEV引起血压显著升高。我们建议测试一下 SEV参与血管调节的一般假设 抵抗力和肾功能。此外，该委员会的一名不知名成员 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发挥作用。为了进一步 我们对这些新的激肽释放酶的生理病理作用的理解- 相关的酶，我们建议：i)：在组织中定位SEV及其mRNA 利用聚合酶链式反应，原位杂交， 免疫组织化学和放射免疫分析。此外，我们将确定是否 血管组织包含SEV的结合部位以及SEV是否释放 血管收缩肽(S)；II)：确定：a)是否释放SEV 作为一种内分泌和/或外分泌激素。我们将研究将SEV释放到 颌下腺的唾液和尿液 分别在肾脏和这些器官的静脉流出物中 调节组织中SEV及其基因表达的因子(S) 级别。三)：确定急性注射SEV对以下方面的影响 血压、心输出量和肾功能，以及是否阻断 带有单抗Fab片段的内源性SEV改变任何 这些参数。四)：鉴定、提纯和表征 激肽释放酶相关蛋白在大鼠血管极的表达 肾小球。

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.