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Interference of the Paf antagonist Ro 19–3704 with Paf and antigen‐induced bronchoconstriction in the guinea‐pig
Author(s) -
Lagente Vincent,
Desquand Stéphanie,
Hadvary Paul,
Cirino Maria,
LellouchTubiana Arielle,
Lefort Jean,
Vargaftig B. Boris
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11496.x
Subject(s) - bronchoconstriction , platelet activating factor , ovalbumin , chemistry , antagonist , superoxide , medicine , endocrinology , guinea pig , pharmacology , immunology , antigen , biochemistry , receptor , asthma , enzyme
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.