2-Furoyl-LIGRLO-amide: A potent and selective proteinase-activated receptor 2 agonist

A peptide corresponding to a proteinase-activated receptor 2 (PAR(2))-activating peptide with an N-terminal furoyl group modification, 2-furoyl-LIGRLO-NH2, was assessed for PAR(2)-dependent and -independent biological activities. 2-Furoyl-LIGRLO-NH2 was equally effective to and 10 to 25 times more potent than SLIGRL-NH2 for increasing intracellular calcium in cultured human and rat PAR(2)-expressing cells, respectively. In bioassays of tissue PAR(2) activity, measured as arterial vasodilation and hyperpolarization, 2-furoyl-LIGRLO-NH2 was 10 to 300 times more potent than SLIGRL-NH2. Unlike trans-cinnamoyl-LIGRLO-NH2, 2-furoyl-LIGRLO-NH2 did not cause a prominent non-PAR(2)-mediated contraction of murine femoral arteries. In conclusion, 2-furoyl-LIGRLO-NH2 represents the most potent and selective activator of PAR(2) in biological systems described to date.