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BACKGROUND AND PURPOSE Many cells express proteinase activated receptor 2 (PAR2) on their plasma membrane. PAR2 is activated by proteolytic enzymes, such as trypsin and tryptase that cleave the receptor N‐terminus, inititating signalling to intracellular G proteins. Studies on PAR2 have relied heavily upon activating effects of proteases and peptide agonists that lack stability and bioavailability in vivo.

EXPERIMENTAL APPROACH A novel small molecule agonist GB110 and an antagonist GB88 were characterized in vitro against trypsin, peptide agonists, PAR2 antibody, PAR1 agonists and flow cytometry,in seven cell lines using intracellular Ca²⁺ mobilization and examined in vivo against PAR2‐ and PAR1‐induced rat paw oedema.

KEY RESULTS GB110 is a potent non‐peptidic agonist activating PAR2‐mediated Ca²⁺ release in HT29 cells (EC₅₀∼200 nM) and six other human cell lines, inducing …