Differential inhibition by two hetrazepine PAF antagonists of acute inflammation in the mouse.
1. The injection of 100 or 300 micrograms of carrageenin into the mouse paw or pleural cavity produced a delayed inflammatory reaction at 48 h while platelet activating factor (PAF)-induced paw oedema and pleurisy were maximal 30 min after its injection. 2. The PAF antagonist, WEB 2086, failed to inhibit mouse paw oedema and pleurisy induced by PAF, but reduced the first phase of oedema (1-4 h) induced by carrageenin without interfering with the second one (48-72 h). In contrast, another structurally-related PAF antagonist, WEB 2170, inhibited dose-dependently both oedema and pleurisy induced by PAF and by carrageenin (48 h). 3. Repeated injections of PAF into the mouse paw or pleural cavity led to significant autodesensitization. The animals desensitized to PAF and injected with carrageenin also displayed a significantly reduced oedema. 4. Our results suggest that PAF may be involved in the inflammatory response to carrageenin in mice. Furthermore, because the different receptor antagonists displayed distinct effects against PAF itself, different sites for in vivo interaction of PAF are available and are species- and drug-dependent.
Henriques
M G
MG
Dept. Fisiologia e Farmacodinâmica, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Weg
V B
VB
Martins
M A
MA
Silva
P M
PM
Fernandes
P D
PD
Cordeiro
R S
RS
Vargaftig
B B
BB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines / Q000494:pharmacology*; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005122:Exudates and Transudates / Q000378:metabolism; D005260:Female; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy; D012701:Serotonin / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines; D010972:Platelet Activating Factor; D014227:Triazines; D014230:Triazoles; C052518:WEB 2086; D012701:Serotonin; D002351:Carrageenan; C063964:bepafant