Interference of the Paf antagonist Ro 19-3704 with Paf and antigen-induced bronchoconstriction in the guinea-pig.
|
| Abstract |
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.
|
|---|---|
| Authors | V Lagente, S Desquand, P Hadvary, M Cirino, A Lellouch-Tubiana, J Lefort, B B Vargaftig |
| Journal | British journal of pharmacology (Br J Pharmacol) Vol. 94 Issue 1 Pg. 27-36 (May 1988) ISSN: 0007-1188 [Print] England |
| PMID | 3401641 (Publication Type: Journal Article) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!