DIFFERENTIAL INHIBITION BY 2 HETRAZEPINE PAF ANTAGONISTS OF ACUTE-INFLAMMATION IN THE MOUSE

The injection of 100 or 300 μg 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. The PAF antagonist, WEB2086, 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, WEB2170, inhibited dose-dependently both eodema and pleurisy induced by PAF and by carrageenin (48 h). Repeated injections of PAF into the mouse paw or pleural cavity led to significant auto-desensitization. The animals desensitized to PAF and injected with carrageenin also displayed a significantly reduced oedema. 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.