title: A lethal role of platelet activating factor in anaphylactic shock in mice.
abstract: The lethal role of platelet activating factor (PAF) in anaphylactic shock was examined in mice, using the specific PAF antagonist, CV-3988. CV-3988 (0.3-3 mg/kg i.v.), given 5 min before PAF, protected mice from death (ED50, 0.9 mg/kg). CV-3988 (3 mg/kg i.v.), given 1 min after PAF was injected, was also effective, but no so effective when given 5 min later. Dexamethasone (2 mg/kg i.v. 3 hr before the PAF-injection), naloxone (1 and 10 mg/kg i.v. 5 min before), FPL-55712 (10 mg/kg i.v. 5 min before) and BW-755c (300 mg/kg p.o. 1 hr before) also improved the survival rate, but aspirin (100 mg/kg p.o. 1 hr before) did not. In anaphylactic shock, CV-3988 (0.3-3 mg/kg i.v.), given 5 min before and 5 min after rechallenge with antigen protected the sensitized mice from death (ED50, 1.2 and 0.48 mg/kg, respectively). Dexamethasone and naloxone protected mice from anaphylactic shock, but BW-755c and FPL-55712 had no protective effects. In contrast to CV-3988, dexamethasone and naloxone were ineffective when given 5 min after the rechallenge. Congestion of the lung, kidney and heart and infiltration of neutrophils in the lung were marked in mice with PAF-induced and anaphylactic shock. The related histology showed an improvement with CV-3988. These results strongly suggest that PAF may play a lethal role in anaphylactic shock and that CV-3988 may be an effective preventing agent.
mesh_terms: D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000707:Anaphylaxis / Q000517:prevention & control; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000494:pharmacology; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000276:immunology*; D011720:Pyrazoles / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors; D013844:Thiazoles / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002867:Chromones; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D011720:Pyrazoles; D013189:SRS-A; D013844:Thiazoles; D009270:Naloxone; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D003907:Dexamethasone; C037913:CV 3988; C006312:FPL 55712; D001241:Aspirin