Pharmacological modulation of Paf-induced rat pleurisy and its role in inflammation by zymosan.

Abstract

1. The intrapleural injection of Paf-acether into rats caused, at 30 min, a marked exudation accompanied by a reduction in the pleural leucocyte count. At 6 h, the exudate volume had decreased and a significant increase in the total leucocyte count, particularly eosinophils was noted. 2. Two Paf-acether antagonists, WEB 2086 and 48740 RP abrogated the pleural leucopenia observed 30 min after Paf-acether administration, whereas the exudation was inhibited only by the former. Pleurisy was also reduced by about 60% with dexamethasone, by about 45% with BW 755C or LY 171883, a mixed cyclo-oxygenase/lipoxygenase inhibitor and a peptido-leukotriene antagonist respectively, and by about 30% with indomethacin, flurbiprofen or piroxicam. 3. Repeated daily intrapleural injections of Paf-acether led to a state of progressive desensitization to Paf-acether itself, whereas responsiveness to 5-hydroxytryptamine was maintained. In addition, the Paf-induced auto-desensitization was largely inhibited by WEB 2086. 4. Pleurisy induced by zymosan, but not by carrageenin, was significantly reduced in Paf-acether-desensitized animals. These results were consistent with those obtained with WEB 2086 which suppressed zymosan-induced but not carrageenin-induced pleurisy. 5. This study suggests that Paf-acether-induced pleurisy in the rat may be mediated by lipoxygenase arachidonic acid metabolites and that pleurisy induced by zymosan, but not by carrageenin, is largely dependent upon Paf-acether.

• Authors: M A Martins, P M Silva, H C Faria Neto, P T Bozza, P M Dias, M C Lima, R S Cordeiro, B B Vargaftig
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 96 Issue 2 Pg. 363-71 (Feb 1989) ISSN: 0007-1188 [Print] England
• PMID: 2924083 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Azepines
• Platelet Activating Factor
• Pyridines
• Thiazoles
• Triazines
• Triazoles
• WEB 2086
• Carrageenan
• Zymosan
• 3-(3-pyridinyl)-1H,3H-pyrrolo(1,2-c)thiazole-7-carboxamide

Topics

• Animals
• Azepines (pharmacology)
• Carrageenan (antagonists & inhibitors, toxicity)
• Leukocyte Count
• Male
• Platelet Activating Factor (antagonists & inhibitors)
• Pleurisy (chemically induced, prevention & control)
• Pyridines (pharmacology)
• Rats
• Rats, Inbred Strains
• Thiazoles (pharmacology)
• Triazines (pharmacology)
• Triazoles
• Zymosan (antagonists & inhibitors, toxicity)