Effect of the PAF antagonists, CV-3988 and L-652,731 on the pulmonary and hematological responses to guinea pig anaphylaxis.
To define the role of PAF in the acute phase of guinea pig anaphylaxis, we have measured the pulmonary (bronchoconstrictor) and hematological (thrombocytopenia, leukopenia, hemoconcentration, plasma TxB2 increase) responses to PAF infusion and compared these responses to the effect of antigen exposure in actively and passively sensitized guinea pigs. We have also determined the effect of the structurally unrelated PAF antagonists, CV-3988 and L-652,731 on these responses. Intravenous administration of PAF (50-400 ng/kg) caused a dose-related bronchoconstriction, thrombocytopenia, leukopenia, hemoconcentration and increase in plasma TxB2. These PAF-induced responses were inhibited, to a variable degree, by pretreatment with CV-3988 (3 and 10 mg/kg, i.v.) and L-652,731 (3 mg/kg, i.v.). Intravenous administration of ovalbumin to actively or passively sensitized guinea pigs caused bronchoconstriction, thrombocytopenia, leukopenia and hemoconcentration, but there was no increase in TxB2. Moreover, the anaphylactic bronchoconstriction, thrombocytopenia, leukopenia (actively sensitized) and hemoconcentration were not inhibited by CV-3988 (10 mg/kg, i.v.) and L-652,731 (3 mg/kg, i.v.). The different profile of changes produced by PAF and allergic anaphylaxis and the failure to alter the responses to allergic anaphylaxis with PAF antagonists suggest that PAF is not an important mediator of the acute phase of guinea pig anaphylaxis.
Danko
G
G
Department of Allergy and Inflammation, Schering-Plough Corporation, Bloomfield, New Jersey 07003.
Sherwood
J E
JE
Grissom
B
B
Kreutner
W
W
Chapman
R W
RW
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D001773:Blood Cells / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D005663:Furans / Q000494:pharmacology*; D006168:Guinea Pigs; D006400:Hematocrit; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*
D005663:Furans; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; C037913:CV 3988; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran