Fever-like temperature modification differentially affects in vitro signaling of bradykinin B₁ and B₂ 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 Cb (PLCb) and mitogen activated protein kinase (MAPK) signaling. Because inflammatory processes are characterized by heat (fever), we analyzed the effect of increased temperature (418C vs. 378C) 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 PLCb activity and Ca 2q -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 418C for both receptors. Taken together, our findings suggest that the observed temperature sensitivity of B 1 R-induced PLCb 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.

RNA-seq analysis of broiler liver transcriptome reveals novel responses to high ambient temperature

“…Texel and Mattson [ 53 ] reported that excess amyloid β fibril formation perturbed calcium homeostasis in mouse neuronal cells, possibly triggering apoptosis from calcium overload. BDKRB1 encodes for a bradykinin receptor that belongs to the rhodopsin-like GPRs that function in the regulation of inflammation [ 54 ]. The activation of BDKRB1 increases cytosolic calcium levels [ 55 ].…”

10 Kallikrein-Kinin Cascade: Bioregulation by Human Tissue Kallikrein 1 (hK1, KLK1)

“…Increases in intracellular cAMP levels, often observed after addition of BK, are, almost exclusively, caused indirectly through stimulation of G s -coupled prostaglandin receptors. Activation of kinin receptors also results in the stimulation of mitogen-activated protein kinases (MAPK) cascades, with coupling to G-proteins G q/11 and G i/o being required for efficient stimulation of the ERK1/2 MAPK pathway by both B 2 R and B 1 R (Calixto et al, 2004;Leschner et al, 2011).…”

New Insights into the Role of Glutathione in the Mechanism of Fever

“…Although PGE 2 is fundamental in the febrile response, some cytokines and other inflammatory mediators may activate fever independent of PGE 2 [44]. Other than PGE 2 , inflammatory mediators that may disrupt thermal balance include bradykinin [45], corticotropin releasing hormone [46], nitric oxide [47], macrophage inflammatory protein1 (MIP-1) [48], endothelin [49], preformed pyrogenic factors (PFPF), and substance P [6,44]. The pyrogenic signal that is generated as a result of peripheral inflammatory challenge is likely transmitted to the brain where responses can be generated to cause a rise in body temperature [43].…”