Effects of tumor necrosis factor alpha on beta-adrenoceptor and beta-adrenoceptor related GRKs in rat PMVEC
- VernacularTitle:TNF-?对大鼠肺微血管内皮细胞?-受体及其相关GRKs的影响
- Author:
Zhenliang XIAO
;
Guisheng QIAN
;
Gengyun SUN
;
- Publication Type:Journal Article
- Keywords:
tumor necrosis factor alpha;
beta adrenoceptor;
G protein coupled receptor kinase;
microvascular endothelial cell;
rat
- From:Journal of Third Military Medical University
2003;0(10):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of tumor necrosis factor ? (TNF ?) on ? adrenoceptor (? AR) and ? AR related G protein coupled receptor kinases (GRKs) in rat pulmonary microvascular endothelial cells (PMVECs) as well as the interfering action of anisodamine. Methods Radio ligand binding assay was used to measure the maximal binding capacity (B max ) changes of ? AR in rat PMVECs after treatment with TNF ?. The effects of TNF ? and ? AR related GRKs expression at the protein level were observed by Western blotting. Results B max of ? AR in normal rat PMVECs was (5.58?0.31) fmol/10 5 cells. B max of ? AR in TNF ? group decreased significantly as compared with that in the normal control group, but no significant difference was found between the normal control group and TNF ?+anisodamine group. The expression of GRK2 in rat PMVECs was positive, but expression of GRK3, GRK5, and GRK6 were negative. The expression of GRK2 in TNF ? group and TNF ?+anisodamine group increased significantly as compared with that in the normal control group, but no significant difference was found between the TNF ? group and the TNF ?+anisodamine group. Conclusion GRK2 but not GRK3, GRK5, or GRK6 is expressed in rat PMVECs. The increased expression of GRK2 induced by TNF ? in rat PMVECs might promote the phosphorylation of ? AR, leading to ? AR internalization and decoupling with G protein, which might be the main mechanism of down regulation of ? AR induced by TNF ?. Anisodamine might inhibit the down regulation of ? AR through other mechanism instead of inhibiting the increase of GRK2 expression.
