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Characterization of the inflammatory response to proteinase‐activated receptor‐2 (PAR 2 )‐activating peptides in the rat paw
Author(s) -
Vergnolle Nathalie,
Hollenberg Morley D,
Sharkey Keith A,
Wallace John L
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702634
Subject(s) - chemistry , inflammation , receptor , nitric oxide , mast cell , pharmacology , nitric oxide synthase , infiltration (hvac) , substance p , peptide , medicine , endocrinology , immunology , biochemistry , neuropeptide , physics , organic chemistry , thermodynamics
In the present study, we have observed the development of an inflammatory reaction in the rat hindpaw, following the injection of specific agonists of PAR 2 (two PAR 2 activating peptides). This inflammation was characterized by oedema and granulocyte infiltration. Two selective PAR 2 activating peptides, SLGRL‐NH 2 and trans ‐cinnamoyl‐LIGRLO‐NH 2 induced significant oedema in the rat hindpaw from 1–6 h following subplantar injection. Six hours after the PAR 2 ‐activating peptide injection, the paw tissues showed a complete disruption of tissue architecture along with an inflammatory cell infiltrate. In the inflamed paw, PAR 2 ‐immunoreactivity was expressed on endothelial cells as well as on the infiltrating inflammatory cells. The oedema induced by the injection of the two PAR 2 activating peptides was slightly reduced in rats pre‐treated with compound 48/80, but was not modified by pre‐treatment of rats with cromolyn, a mast cell stabilizer. Pre‐treatment of rats with a cyclo‐oxygenase inhibitor (indomethacin) or a nitric oxide synthase inhibitor ( L ‐N ω ‐nitro‐ L ‐arginine methyl ester) had no effect on the oedema induced by the PAR 2 ‐activating peptides. These results demonstrate that the administration of PAR 2 ‐activating peptides into the rat paw induced an acute inflammatory response characterized by a persistent oedema (at least 6 h) and granulocyte infiltration. The PAR 2 ‐induced inflammatory response occurred through a mechanism largely independent of mast cell activation, and of the production of prostanoids and nitric oxide.British Journal of Pharmacology (1999) 127 , 1083–1090; doi: 10.1038/sj.bjp.0702634