Screening of angiotensin type 1 receptor blockers with the function to activate peroxisome proliferator-activated receptor ? and ?
- VernacularTitle:具PPAR?和PPAR?双重激动作用的ARB类药物的筛选
- Author:
Shinan YIN
;
Danqing JING
;
Yiming MU
- Publication Type:Journal Article
- Keywords:
PPAR?;
PPAR?;
telmisartan;
irbesartan
- From:
Medical Journal of Chinese People's Liberation Army
1983;0(02):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explorer the effect of angiotensin type 1 receptor blockers (ARB) on activating peroxisome proliferator-activated receptor (PPAR) ? and ?.MethodsLuciferase gene reporters of PPAR? and PPAR? were constructed in COS-7 cells.The cells were then cultured with various concentrations (0,0.01,0.1,1,10 and 100 ?mol/L) of valsartan,losartan,irbesartan or telmisartan for 12,24,36,48 and 60 hours;or co-cultured with PPAR? antagonist GW9662 (10,30?mol/L) for 1 hour,and then cultured with various concentrations (0,1 and 10?mol/L) of irbesartan or telmisartan for 12,24,36,48 and 60 hours.The peroxisome proliferator-response element (PPRE) luciferase activity was determined by Dual-Luciferase Reporter Gene Assay system.3T3-L1 cells were induced to differentiate into adipocytes,and then co-cultured with 10?mol/L of valsartan,losartan,irbesartan or telmisartan for 24 hours,and the expressions of PPAR? and PPAR? mRNA and protein were detected by RT-PCR and Western blotting respectively.ResultsStimulation of valsartan and losartan didn't increase the transcriptional activities of PPAR? and PPAR? in COS-7 cells,while of irbesartan and telmisartan significantly increased the transcriptional activity of PPAR? and PPAR? in COS-7 cells.After co-cultured with 100 ?mol/L of irbesartan or telmisartan for 48 hours,the PPAR? transcriptional activities reached their peak values (43.3?13.0 and 47.8?11.8 respectively),and were significantly higher than that of control group (4.3?0.5,P
