RENAL ENZYMES THAT REGULATE BLOOD PRESSURE

调节血压的肾酶

• 批准号: 3350700
• 负责人: ERVIN G ERDOS
• 金额: $ 13.15万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3350700
• 关键词: acidity /alkalinity; aldosterone; angiotensin II; cell membrane; diuretics; endoplasmic reticulum; gel electrophoresis; human tissue; ionic strengths; kallikreins; kidney; kidney pharmacology; laboratory rat; radioimmunoassay; renal hypertension; renin; reserpine; spironolactone

The investigations of renal enzymes and their activators will be continued with emphasis on tissue kallikrein and renin. Although these enzymes are concentrated in the kidney, they are present in other organs as well. The recent developments in deciphering the structure of pro-renin and prokallikrein make it possible to establish the mode of activation and identify endogenous activating enzymes of the inactive pro-enzymes. The activation of both homogeneous prokallikrein and prokallikrein hound to cell membranes will be studied. With purified prokallikrein, activation will be correlated with the N-terminal sequence in order to determine how the removal of one or more N-terminal amino acids during activation could affect enzymatic activity and antigenicity. The subcellular site of activation of prokallikrein will be localized by adopting a novel technique combining immunohistochemistry with ultra- structural studies. The search for endogenous tissue activating enzymes for both prokallikrein and prorenin will continue. The site of activation in the peptide chain of prorenin and the resulting N-terminal sequence of the enzyme will be characterized. The length of the N-terminal propeptide residue still present after the activation will be correlated with the renin activity. The studies on the activation of prokallikrein and prorenin will bring about a better understanding of the two frequently oppositely acting systems, which can control normal and abnormal blood pressure.

肾酶及其激活剂的研究将是 继续强调组织激肽释放酶和肾素。 虽然 这些酶集中在肾脏中，它们存在于 其他器官也是。 最近在破译 原肾素和原激肽释放酶结构使得有可能 建立激活模式，识别内源性激活 非活性前酶的酶。 两者的活化作用 均质原激肽释放酶和原激肽释放酶结合细胞膜 将被研究。 使用纯化的原激肽释放酶， 与N-末端序列相关，以确定如何 在活化过程中除去一个或多个N-末端氨基酸 可能影响酶活性和抗原性。 亚细胞 原激肽释放酶的激活位点将通过采用 一种新的免疫组织化学和超 结构研究。 寻找内源性组织激活 用于前激肽释放酶和前肾素的酶将继续。 的 在前肾素的肽链中的活化位点和 将表征所得到的酶的N-末端序列。 N-末端前肽残基的长度在 激活将与肾素活性相关。 的 对前激肽释放酶和前肾素活化的研究将带来 关于更好地理解这两个经常相反的 作用系统，可以控制正常和异常的血液 压力