title: Fever-like temperature modification differentially affects in vitro signaling of bradykinin B(1) and B(2) receptors.
abstract: The bradykinin (BK) B(2) and B(1) receptors (B(2)R, B(1)R) 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 B(2)R is constitutively expressed and gets internalized upon activation, the B(1)R is especially induced by inflammatory mediators and responds to stimulation with increased surface receptor numbers. Stimulation of both receptors activates phospholipase Cβ (PLCβ) and mitogen activated protein kinase (MAPK) signaling. Because inflammatory processes are characterized by heat (fever), we analyzed the effect of increased temperature (41°C vs. 37°C) on B(1)R and B(2)R 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 PLCβ activity and Ca(2+)-regulated signals, a temperature-dependent increase was only observed for B(1)R but not for B(2)R activation, whereas MAPK activities were doubled at 41°C for both receptors. Taken together, our findings suggest that the observed temperature sensitivity of B(1)R-induced PLCβ activation is B(1)R-specific. In contrast, the enhanced stimulation of MAPK activity under hyperthermic conditions appears to be a common phenomenon for GPCRs.
authors.affiliation: Abteilung für Klinische Chemie und Klinische Biochemie, Ludwig-Maximilians-Universität, Nussbaumstrasse 20, D-80336 München, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Leschner
authors.forename: Larisa
authors.initials: L
authors.lastname: Ring
authors.forename: Jens
authors.initials: J
authors.lastname: Feierler
authors.forename: Klaus
authors.initials: K
authors.lastname: Dinkel
authors.forename: Marianne
authors.initials: M
authors.lastname: Jochum
authors.forename: Alexander
authors.initials: A
authors.lastname: Faussner
mesh_terms: D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D005334:Fever / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D054799:Phospholipase C beta / Q000378:metabolism; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018808:Transcription Factor AP-1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054799:Phospholipase C beta; D002118:Calcium