Role of Endothelial G Protein-Coupled Receptor Kinase 2 in Angioedema.

ABSTRACT: Excessive BK (bradykinin) stimulation is responsible for the exaggerated permeabilization of the endothelium in angioedema. However, the molecular mechanisms underlying these responses have not been investigated. BK receptors are Gq-protein-coupled receptors phosphorylated by GRK2 (G protein-coupled receptor kinase 2) with a hitherto unknown biological and pathophysiological significance. In the present study, we sought to identify the functional role of GRK2 in angioedema through the regulation of BK signaling. We found that the accumulation of cytosolic Ca²⁺ in endothelial cells induced by BK was sensitive to GRK2 activity, as it was significantly augmented by inhibiting the kinase. Accordingly, permeabilization and NO production induced by BK were enhanced, as well. In vivo,

SUBMITTER: Gambardella J 

PROVIDER: S-EPMC7544666 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature