Biochemical characterization of a novel high-affinity and specific plasma kallikrein inhibitor.

ABSTRACT:

Background and purpose

Kallikrein acts on high molecular weight kininogen (HK) to generate HKa (cleaved HK) and bradykinin (BK). BK exerts its effects by binding to B(2) receptors. The activation of B(2) receptors leads to the formation of tissue plasminogen activator, nitric oxide (NO) and prostacyclin (PGI(2) ). An elevated kallikrein-dependent pathway has been linked to cardiovascular disease risk. The aim of this study was to investigate whether our novel plasma kallikrein inhibitor abolishes kallikrein-mediated generation of BK from HK and subsequent BK-induced NO and PGI(2) formation, thereby influencing endothelial pathophysiology during chronic inflammatory diseases.

Experimental approach

Kinetic analysis was initially used to determine the potency of PF-04886847. Bi

SUBMITTER: Kolte D 

PROVIDER: S-EPMC3057299 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature