Pathway-selective antagonism of proteinase activated receptor 2.

ABSTRACT:

Background and purpose

Proteinase activated receptor 2 (PAR2) is a GPCR associated with inflammation, metabolism and disease. Clues to understanding how to block PAR2 signalling associated with disease without inhibiting PAR2 activation in normal physiology could be provided by studies of biased signalling.

Experimental approach

PAR2 ligand GB88 was profiled for PAR2 agonist and antagonist properties by several functional assays associated with intracellular G-protein-coupled signalling in vitro in three cell types and with PAR2-induced rat paw oedema in vivo.

Key results

In HT29 cells, GB88 was a PAR2 antagonist in terms of Ca(2+) mobilization and PKC phosphorylation, but a PAR2 agonist in attenuating forskolin-induced cAMP accumulation, increasing ERK1/2 phosphoryla

SUBMITTER: Suen JY 

PROVIDER: S-EPMC4243983 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature