Insights into G protein signaling capabilities of the Kinin receptors

Abstract ID 128917 Poster Board 366 The kinin receptors are G Protein Coupled Receptors (GPCRs) that mediate the sensation of pain and inflammation. Specifically, there are two types of kinin receptors- Bradykinin-1 (B1) and Bradykinin-2 (B2) receptors. These receptors are activated by four different endogenous peptide agonists namely Bradykinin, Kallidin, Des-Arg-9 Bradykinin (DABK) and Des-Arg 10-Kallidin (DAKD). Activation of the receptors by each of these peptides is translated into distinct intracellular events through the recruitment of diverse heterotrimeric G proteins. However, a comprehensive G protein activation profile of the kinin receptors when activated by these different agonists has not yet been established. This study uses Bioluminescence resonance Energy Transfer (BRET) based in vitro assays that detect direct coupling to 14 different Ga proteins upon B1 and B2 receptor activation. Our results show that there is a shift in G protein activation profiles and kinetics among the different peptides. More specifically, while B2 is activated by all four peptides, B1 activation is limited to DAKD and DABK peptides. Further, analysis over a range of concentrations was employed to elucidate the existence of bias among the different peptides in activating different Ga subunits. These results help better understand the intracellular mechanisms through which the kinin system regulates aspects of pain modulation and provides valuable information for the design of drugs targeting the kinin receptors