Fever-like temperature modification differentially affects in vitro signaling of bradykinin B1 and B2 receptors

被引:8
作者
Leschner, Jasmin [1 ]
Ring, Larisa [1 ]
Feierler, Jens [1 ]
Dinkel, Klaus [2 ]
Jochum, Marianne [1 ]
Faussner, Alexander [1 ]
机构
[1] Univ Munich, Klin Chem & Klin Biochem Abt, D-80336 Munich, Germany
[2] Lead Discovery Ctr GmbH, D-44227 Dortmund, Germany
关键词
AP-1; ERK1/2; fever; GPCR; NFAT; KININ B-1; EXPRESSION; ACTIVATION; MECHANISMS; RESPONSES; PATHWAYS; FAMILY; CELLS;
D O I
10.1515/BC.2011.095
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The bradykinin (BK) B-2 and B-1 receptors (B2R, B1R) belong to the rhodopsin-like G protein-coupled receptors (GPCRs) and are involved in (patho)physiological processes such as blood pressure regulation or inflammation. They mediate the effects of the pro-inflammatory peptides bradykinin/kallidin and desArg(9)-BK/desArg(10)-kallidin, respectively. Whereas the B2R is constitutively expressed and gets internalized upon activation, the B1R is especially induced by inflammatory mediators and responds to stimulation with increased surface receptor numbers. Stimulation of both receptors activates phospholipase C beta (PLC beta) and mitogen activated protein kinase (MAPK) signaling. Because inflammatory processes are characterized by heat (fever), we analyzed the effect of increased temperature (41 degrees C vs. 37 degrees C) on B1R and B2R signaling in HEK 293 and IMR 90 cells. Our results show that signaling of both receptors is temperature-sensitive, however to a different extent and with regard to the investigated pathways. Comparing PLCb activity and Ca2+-regulated signals, a temperature-dependent increase was only observed for B1R but not for B2R activation, whereas MAPK activities were doubled at 41 degrees C for both receptors. Taken together, our findings suggest that the observed temperature sensitivity of B1R-induced PLCb activation is B1R-specific. In contrast, the enhanced stimulation of MAPK activity under hyperthermic conditions appears to be a common phenomenon for GPCRs.
引用
收藏
页码:1021 / 1029
页数:9
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