权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

EFFECT OF CYCLOSPORINE ON PRODUCTION, SECRETION AND METABOLISM OF ENDOTHELIN

环孢素对内皮素产生、分泌和代谢的影响

基本信息

批准号：
5203552
负责人：
Z ABASSI
金额：
--
依托单位：
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/5203552
关键词：
clearance rate cyclosporines endothelin enzyme activity gene expression hormone regulation /control mechanism kidney metabolism kidney pharmacology laboratory rat messenger RNA metalloendopeptidases polymerase chain reaction radiotracer renal failure

项目摘要

We investigated the effects of CsA administration to rats on 1)plasma and urinary levels of ET, 2) expression of ET-1, ET-3 and endothelin converting enzyme (ECE) in renal tissue, 3)clearance of infused 125 I- ET-1, and 4)degradation of 125I-ET-1 by recombinant neutral endopeptidase. Rats given CsA for 6 days developed severe renal insufficiency, e.g., GFR decreased 74%. Urinary excretion of ET increased from an undetectable level to 31.7+6.0pg/24h, while plasma levels of ET were unchanged. Reverse transcription followed by a quantitative polymerase chain reaction (RT-PCR) revealed that ET-1-mRNA in the renal medulla increased 59%, while the expression of both ET-3 and ECE was unchanged. Neither acute nor chronic treatment with CsA affected either the clearance of 125I-ET-1 from the blood or the renal and pulmonary uptake of the peptide. Moreover, CsA did not affect the degradation of 125I-ET-1 by highly purified recombinant neutral endopeptidase, a well known endothelinase. These findings indicate that: 1) the elevated urinary ET levels occurring afer CsA treatment originate from the kidney, and reflect increased renal synthesis of Et, 2) the production of ET is regulated at the level of mRNA transcription, and 3) the expressions of ET-1 and ET-3 are regulated independently.

我们研究了CsA给药对大鼠1）血浆 ET-1、ET-3和ET-1的表达肾组织中的转化酶（ECE）; 3）输注的125I- ET-1，和4）重组中性蛋白酶对125I-ET-1的降解内肽酶大鼠给予CsA 6天后，不足，例如，GFR下降74%。尿ET排泄从检测不到的水平增加到31.7 ± 6.0pg/24h，而血浆 ET水平无变化。逆转录后，定量聚合酶链反应（RT-PCR）显示ET-1-mRNA 肾髓质中ET-3表达增加59%，而欧洲经委会没有变化。既不接受CsA急性治疗，也不接受CsA慢性治疗影响~（125）I-ET-1从血液或肾脏中的清除和肺对肽的摄取。此外，CsA不影响高纯度重组中性粒细胞对125I-ET-1的降解内肽酶，一种众所周知的内皮素酶。提示：1）尿ET水平升高， CsA治疗后发生的肾源性疾病，增加肾脏合成Et，2）调节ET的产生 ET-1和ET-2在mRNA转录水平的表达 ET-3是独立调节的。