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

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 309; no. 3; p. 1124
• Main Authors: McGuire, John J, Saifeddine, Mahmoud, Triggle, Chris R, Sun, Kimberly, Hollenberg, Morley D
• Format: Journal Article
• Language: English
• Published: United States 01-06-2004
• Subjects: Amides - pharmacology; Animals; Aorta - drug effects; Aorta - physiology; Electrophysiology; Femoral Artery; Humans; Male; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiology; Mice; Mice, Inbred C57BL; Oligopeptides - pharmacology; Peptides - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, PAR-2 - agonists; Receptor, PAR-2 - metabolism; Vascular Resistance - drug effects
• ISSN: 0022-3565
• DOI: 10.1124/jpet.103.064584

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.