Modulation of PAR(1) signalling by benzimidazole compounds.

ABSTRACT:

Background and purpose

Recently, a small molecule (Q94) was reported to selectively block PAR(1) /Gα(q) interaction and signalling. Here, we describe the pharmacological properties of Q94 and two analogues that share its benzimidazole scaffold (Q109, Q89). Q109 presents a modest variation from Q94 in the substituent group at the 2-position, while Q89 has quite different groups at the 1- and 2-positions.

Experimental approach

Using human microvascular endothelial cells, we examined intracellular Ca(2+) mobilization and inositol 1,4,5-trisphosphate accumulation as well as isoprenaline- or forskolin-stimulated cAMP production in response to thrombin.

Key results

Q89 (10 µM) produced a leftward shift in the thrombin-mediated intracellular Ca(2+) mobilization concentrat

SUBMITTER: Asteriti S 

PROVIDER: S-EPMC3448915 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature