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Application of angiotensin II-1 type mechanical stress receptor perception site in preparing of medicines for treating hypertension

An angiotensin and hypertension technology, applied in drug combinations, cardiovascular system diseases, pharmaceutical formulations, etc., can solve problems such as inhibiting AT1R activation, improve clinical treatment efficacy, realize big data precision medicine, and inhibit myocardial Effects of hypertrophy and cardiovascular protection

Inactive Publication Date: 2017-03-29
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Increasing experimental evidence from basic research suggests that this level of inhibition is not sufficient to completely suppress AT1R activation

Method used

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  • Application of angiotensin II-1 type mechanical stress receptor perception site in preparing of medicines for treating hypertension
  • Application of angiotensin II-1 type mechanical stress receptor perception site in preparing of medicines for treating hypertension
  • Application of angiotensin II-1 type mechanical stress receptor perception site in preparing of medicines for treating hypertension

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Experimental program
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Embodiment 1

[0027] 1. Materials and methods

[0028] 1. Materials and Reagents

[0029] The COS7 cell line is a cryopreserved cell line preserved in our laboratory. ATG - / - The mice came from the laboratory of Professor Issei Komuro, Chiba University, Japan, and were raised in the SPF animal room of the Experimental Animal Center of Zhongshan Hospital Affiliated to Fudan University. Silicone dish and stretching frame, AT 1 R wild-type and mutant plasmids and adenoviruses (K199Q, L212F, Q257A and C289A) were obtained from the Cardiology Research Laboratory of Chiba University, Japan. Losartan and Ang II were purchased from Sigma, USA. AT 1 The primary antibody of R was purchased from SANTA CRUZ Company of the United States, and the other primary antibodies were purchased from CST Company of the United States. Membrane protein extraction kit was purchased from Merck, Germany. Protein extract (RIPA) and protease inhibitors were purchased from Biyuntian Institute of Biotechnology. DME...

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Abstract

The invention relates to determination of an angiotensin II-1 type receptor perception site. Different AT1R mutants are constructed through an amino acid residue point mutation method to find different pathologic perception sites of AT1R, and the results shows that an Lys199 site of the AT1R is an Ang II perception site, Leu 212 and Cys 289 sites are mechanical stress perception sites, and a Gln 257 site is a common perception site of the Ang II and overloading pressure. By means of determination of the angiotensin II-1 type receptor perception site, design of the new generation of ARB medicines aiming at mechanical stress or the Ang II activated amino acid residue site can be guided, clinical medication can be guided, selective targeting of diseases, such as hypertensively myocardial hypertrophy, mediated by the AT1R is improved, adaptation diseases of the ARB type medicines are evaluated and compared, and the fundamental research of occurrence and development mechanisms of relevant diseases is guided.

Description

technical field [0001] The present invention relates to the technical field of molecular biology and medicine, in particular, relates to the pressure overload of angiotensin II-1 type receptor and the determination of angiotensin II sensing sites, and the activation of the above sites to induce angiotensin II - Application of compounds with altered conformation of type 1 receptors in the preparation of drugs for the treatment of diseases mediated by angiotensin II-1 receptors (such as hypertension, etc.), and the preparation and evaluation of existing drug indications or the occurrence of research-related diseases Application of Reagents to Mechanisms of Development. Background technique [0002] Angiotensin II-type 1 receptor (AT1R) is a member of the family of G protein-coupled receptors (GPCRs) with seven transmembrane structures. The C-terminus transmits biological signals, and then the intracellular second messenger completes the signal transmission relay, and finally ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P9/12C12Q1/02G01N33/533G01N33/569
CPCA61K45/00G01N33/533G01N33/56983
Inventor 邹云增龚惠姜红葛均波蒋国良王时俊杨春杰张国平张莉
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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