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AMINOPEPTIDASE A AND ANGIOTENSIN II METABOLISM

氨基肽酶 A 和血管紧张素 II 代谢

基本信息

批准号：
2378752
负责人：
DENNIS P HEALY
金额：
$ 22.12万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-04-01 至 1998-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2378752
关键词：
ACE inhibitors aminopeptidase angiotensin II cytokine diabetes mellitus dietary sodium enzyme activity enzyme substrate gene expression hormone metabolism hormone receptor hypertension in situ hybridization kidney cell phosphorylation renal glomerulus

项目摘要

DESCRIPTION: (adapted from the abstract) This is an application to study the regulation of the ectopeptidase, aminopeptidase-A (APA) and its potential role in the modulation of local renin-angiotensin systems in the kidney and brain. The basis of the study is the hypothesis that APA is a regulated enzyme whose activity is directly or indirectly modified by angiotensins. Furthermore, it is suggested that the activity of APA is enhanced under conditions in which angiotensin levels are elevated and reduced when angiotensin II (Ang II) levels are low. PKC- and tyrosine kinase-dependent phosphorylations are proposed as biochemical substrates responsible for alterations in APA activity. A corollary hypothesis being addressed is the idea that AIII and not AII may be the critical signaling agent in the CNS and that APA plays a paramount role in this necessary conversion. In order to address these hypotheses, the following specific aims will be addressed: 1) Determine the effects of Ang II infusion, angiotensin converting enzyme inhibition, sodium diet, APA inhibitors and AT1 receptor antagonists on renal expression of APA. 2) Determine whether glomerular APA activity is altered in animals with experimental diabetes or hypertension. 3) Determine the effects of inhibition of APA activity on angiotensin metabolism in the CNS. 4) Determine the role of phosphorylation in regulating APA activity. 5) Determine whether mesangial cell APA activity can be regulated by an Ang II receptor-mediated phosphorylation mechanism. 6)Determine the mechanism by which Ang II or other cytokine/serum factors stimulate APA gene expression in mesangial or renal epithelial cells. 7) Determine if cerebrovascular pericytes express Ang II receptors and contract, in response to Ang II.

描述：（改编自摘要）这是一个应用程序，研究外肽酶、氨肽酶-A（阿帕）和其在调节局部肾素-血管紧张素系统中的潜在作用在肾脏和大脑中。这项研究的基础是假设，阿帕是一种受调节的酶，其活性直接或间接地与由血管紧张素修饰。此外，建议阿帕的活性在血管紧张素当血管紧张素II（Ang II）水平升高或降低时，很低 PKC和酪氨酸激酶依赖性磷酸化是建议作为生化底物负责修改在阿帕活动中。一个必然的假设是这样的想法 AIII而不是AII可能是CNS中的关键信号剂阿帕在这一必要的转变中发挥着至关重要的作用。为了解决这些假设，以下具体目标将解决：1）确定血管紧张素II输注的影响，血管紧张素转换酶抑制，钠饮食，阿帕抑制剂 AT 1受体拮抗剂对阿帕肾表达的影响。 2)确定是否肾小球阿帕活性改变的动物，实验性糖尿病或高血压。 3)确定影响抑制阿帕活性对CNS中血管紧张素代谢的影响。四、确定磷酸化在调节阿帕活性中的作用。第五章）确定系膜细胞是否阿帕活性可以是调节由血管紧张素II受体介导的磷酸化机制。 6)确定血管紧张素II或其他细胞因子/血清刺激阿帕基因在系膜或肾组织中表达的因子上皮细胞 7)确定脑血管周细胞是否表达血管紧张素Ⅱ受体和合同，在响应血管紧张素Ⅱ。

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Aminopeptidase-A. I. CDNA cloning and expression and localization in rat tissues.

氨肽酶-A。

DOI：
10.1152/ajpregu.2000.278.2.r413
发表时间：
2000
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
Troyanovskaya,M;Jayaraman,G;Song,L;Healy,DP
通讯作者：
Healy,DP

Fenoldopam is a partial agonist at dopamine-1 (DA1) receptors in LLC-PK1 cells.