Pharmacological modulation of Paf-induced rat pleurisy and its role in inflammation by zymosan.
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.
Martins
M A
MA
Dept. Fisiologia e Farmacodinâmica, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Silva
P M
PM
Faria Neto
H C
HC
Bozza
P T
PT
Dias
P M
PM
Lima
M C
MC
Cordeiro
R S
RS
Vargaftig
B B
BB
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002351:Carrageenan / Q000037:antagonists & inhibitors / Q000633:toxicity; D007958:Leukocyte Count; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010998:Pleurisy / Q000139:chemically induced / Q000517:prevention & control*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology*; D014230:Triazoles; D015054:Zymosan / Q000037:antagonists & inhibitors* / Q000633:toxicity
D001381:Azepines; D010972:Platelet Activating Factor; D011725:Pyridines; D013844:Thiazoles; D014227:Triazines; D014230:Triazoles; C052518:WEB 2086; D002351:Carrageenan; D015054:Zymosan; C052520:3-(3-pyridinyl)-1H,3H-pyrrolo(1,2-c)thiazole-7-carboxamide