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Desensitization to PAF-induced rat paw oedema by repeated intraplantar injections
Authors:R S Cordeiro  M A Martins  P M Silva  H C Faria Neto  J R Castanheira  B B Vargaftig
Affiliation:3. Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-5158, USA;1. Dipartimento di Scienze della Vita e dell''Ambiente, Universita'' Politecnica delle Marche, Ancona, Italy;2. Department of Immunology and The Center for Cancer Immunology Research, The University of Texas Graduate School for Biomedical Sciences at Houston, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
Abstract:The intraplantar injection of PAF-acether (PAF), induced acute oedema in the rat paw, and desensitized it to subsequent challenges with the same agonist, but not to serotonin. The desensitization was maximal (up to 80% of initial response) after seven consecutive daily injections. In this condition, PAF-induced oedema of the contralateral paw was maintained. The analogue 2-methyl carbamate-PAF (2MC-PAF) was more effective than PAF as a desensitizing agent. Furthermore, the PAF-desensitized paw was refractory to challenges with 2-MC and vice-versa. PAF-acether, but not serotonin-induced rat paw oedema was inhibited by previous intravenous injection of PAF. Intravenous injections of serotonin were also effective in inhibiting selectively serotonin-induced paw oedema, but it was not possible to induce desensitization by repeated intraplantar injections of serotonin. Desensitization to PAF or the pre-treatment with the PAF antagonist BN 52021 did not block the edematogenic response induced by carrageenan.
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