1. Academic Validation
  2. 2-furoyl-LIGRLO-amide: a potent and selective proteinase-activated receptor 2 agonist

2-furoyl-LIGRLO-amide: a potent and selective proteinase-activated receptor 2 agonist

  • J Pharmacol Exp Ther. 2004 Jun;309(3):1124-31. doi: 10.1124/jpet.103.064584.
John J McGuire 1 Mahmoud Saifeddine Chris R Triggle Kimberly Sun Morley D Hollenberg
Affiliations

Affiliation

  • 1 Cardiovascular Research Group, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3V6. [email protected]
Abstract

A peptide corresponding to a proteinase-activated receptor 2 (PAR(2))-activating peptide with an N-terminal furoyl group modification, 2-furoyl-LIGRLO-NH(2), was assessed for PAR(2)-dependent and -independent biological activities. 2-Furoyl-LIGRLO-NH(2) was equally effective to and 10 to 25 times more potent than SLIGRLNH(2) 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-NH(2) was 10 to 300 times more potent than SLIGRL-NH(2). Unlike trans-cinnamoyl-LIGRLO-NH(2), 2-furoyl-LI-GRLO-NH(2) did not cause a prominent non-PAR(2)-mediated contraction of murine femoral arteries. In conclusion, 2-furoyl-LI-GRLO-NH(2) represents the most potent and selective activator of PAR(2) in biological systems described to date.

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