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• W2028455206 abstract "We evaluated a potential role for proteinase‐activated receptor 4 (PAR 4 ) in a rodent paw inflammation model, with a focus on two main features of inflammation: (1) oedema and (2) granulocyte recruitment. A PAR 4 antagonist (Pepducin P4pal‐10; palmitoyl‐SGRRYGHALR‐NH 2 ) reduced both the oedema and granulocyte recruitment induced by a localized administration of carrageenan in the rat hind paw, pointing to a key role for PAR 4 in this inflammation model. Further, intraplantar injection in the mouse hind paw of a PAR 4 agonist (AYPGKF‐NH 2 ), but not its standard PAR 4 ‐inactive peptide control (YAPGKF‐NH 2 ), caused an inflammatory reaction characterized by oedema (increased paw thickness) and granulocyte recruitment (increased paw myeloperoxidase activity). The PAR 4 agonist‐induced effects were inhibited in mice pretreated with pepducin P4pal10. These PAR 4 agonist‐mediated effects were not affected by pretreatment with inhibitors of either NO production or prostaglandin release ( L ‐NAME and indomethacin, respectively). However, selective immuno‐depletion of neutrophils significantly reduced PAR 4 agonist‐induced oedema formation. Moreover, AYPGKF‐NH 2 ‐induced oedema was also reduced by pretreatment with either a kinin B 2 receptor antagonist (icatibant) or a tissue or plasma kallikrein inhibitor (FE999024 and FE999026, respectively), but not with a kinin B 1 receptor antagonist (SSR240612). We conclude: (1) that PAR 4 plays an important role in the inflammatory response as it mediates some of the hallmarks of inflammation and (2) that PAR 4 ‐mediated oedema is dependent on the recruitment of neutrophils and components of the kallikrein–kinin system. British Journal of Pharmacology (2005) 146 , 670–678. doi: 10.1038/sj.bjp.0706371" @default.
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• W2028455206 date "2005-11-01" @default.
• W2028455206 modified "2023-10-13" @default.
• W2028455206 title "Neutrophils and the kallikrein-kinin system in proteinase-activated receptor 4-mediated inflammation in rodents" @default.
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• W2028455206 doi "https://doi.org/10.1038/sj.bjp.0706371" @default.
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