Interference of the Paf antagonist Ro 19-3704 with Paf and antigen-induced bronchoconstriction in the guinea-pig.
1. In vitro, Ro 19-3704, a structurally related antagonist of platelet-activating factor (Paf) inhibited selectively rabbit platelet aggregation. In vivo, administered intravenously, it inhibited bronchoconstriction, leukopenia, thrombocytopenia and the accompanying accumulation of platelet aggregates in guinea-pig lung microvessels induced by i.v. Paf. Administered by aerosol, Ro 19-3704 failed to inhibit bronchoconstriction, thrombocytopenia or leukopenia due to i.v. Paf. 2. Bronchoconstriction induced by Paf, in aerosol form, was blocked by Ro 19-3704 administered by the i.v. or aerosol route, which suggests that it interacts with pulmonary cells responsible for bronchoconstriction. 3. Ro 19-3704 has free radical scavenging properties, since it inhibited the production of superoxide anions by macrophages stimulated by Paf and by N-formyl-methionyl-leucyl-phenylalanine (FMLP). Ro 18-7715, another Paf antagonist and analogue of Ro 19-3704, failed to inhibit the production of superoxide anions by macrophages stimulated by FMLP at concentrations which were effective against Paf. 4. Administered intravenously, Ro 19-3704 failed to block bronchoconstriction induced by an i.v. injection of ovalbumin to guinea-pigs passively sensitized with anti-ovalbumin antiserum. Passive pulmonary anaphylaxis due to an aerosol of ovalbumin was blocked by i.v. Ro 19-3704.
Lagente
V
V
Unité de Pharmacologie Cellulaire, Unité associée Institut Pasteur/INSERM U 285, Paris, France.
Desquand
S
S
Hadvary
P
P
Cirino
M
M
Lellouch-Tubiana
A
A
Lefort
J
J
Vargaftig
B B
BB
D000336:Aerosols; D000818:Animals; D001772:Blood Cell Count; D001993:Bronchodilator Agents / Q000494:pharmacology*; D005260:Female; D005995:Glyceryl Ethers / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011650:Pulmonary Alveoli / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*
D000336:Aerosols; D001993:Bronchodilator Agents; D005995:Glyceryl Ethers; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D013844:Thiazoles; C053235:Ro 19-3704; C037913:CV 3988; D010047:Ovalbumin