Article date: June 1989
By: Sandra Brunelleschi, Daniela Renzi, Fabrizio Ledda, Alberto Giotti, Roberto Fantozzi, Charles Brink, Jacques Benveniste in Volume 97, Issue 2, pages 469-474
The thienotriazolodiazepine WEB 2086 and the gingkolide BN52021 have been evaluated as antagonists of Paf‐acether (Pal) by studying their effects on Paf‐induced relaxation and Paf‐induced prostaglandin E2 (PGE2) production in histamine‐contracted guinea‐pig tracheal preparations.
Relaxation induced by Paf 4 μm in histamine‐contracted guinea‐pig tracheal preparations was 39.67 ± 3.5% (n = 30). At the same concentration, Paf significantly increased PGE2 production from histamine‐contracted guinea‐pig tracheal preparations.
WEB 2086 inhibited in a dose‐related manner (IC50 = 21.2 nm) the relaxant effect induced by Paf and, at 1 μm, suppressed Paf‐induced release of PGE2.
BN 52021 100 μm inhibited to about 60% Paf‐induced relaxation of histamine‐contracted guinea‐pig tracheal preparations, but completely abolished Paf‐induced increase in PGE2.
Both antagonists had no effects on relaxations induced by arachidonic acid 10 μm or PGE2 0.1–1 μm in histamine‐contracted guinea‐pig tracheal preparations.
The results are consistent with the presence of specific Paf receptors in guinea‐pig trachea and indicate that a relaxant prostanoid, namely PGE2, at least partially mediates Paf‐induced relaxation in this experimental model.
The thienotriazolodiazepine WEB 2086 and the gingkolide BN52021 have been evaluated as antagonists of Paf‐acether (Pal) by studying their effects on Paf‐induced relaxation and Paf‐induced prostaglandin E2 (PGE2) production in histamine‐contracted guinea‐pig tracheal preparations.
Relaxation induced by Paf 4 μm in histamine‐contracted guinea‐pig tracheal preparations was 39.67 ± 3.5% (n = 30). At the same concentration, Paf significantly increased PGE2 production from histamine‐contracted guinea‐pig tracheal preparations.
WEB 2086 inhibited in a dose‐related manner (IC50 = 21.2 nm) the relaxant effect induced by Paf and, at 1 μm, suppressed Paf‐induced release of PGE2.
BN 52021 100 μm inhibited to about 60% Paf‐induced relaxation of histamine‐contracted guinea‐pig tracheal preparations, but completely abolished Paf‐induced increase in PGE2.
Both antagonists had no effects on relaxations induced by arachidonic acid 10 μm or PGE2 0.1–1 μm in histamine‐contracted guinea‐pig tracheal preparations.
The results are consistent with the presence of specific Paf receptors in guinea‐pig trachea and indicate that a relaxant prostanoid, namely PGE2, at least partially mediates Paf‐induced relaxation in this experimental model.
DOI: 10.1111/j.1476-5381.1989.tb11974.x
View this article