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  • Title: Interference of WEB 2086 and BN 52021 with Paf-induced effects on guinea-pig trachea.
    Author: Brunelleschi S, Renzi D, Ledda F, Giotti A, Fantozzi R, Brink C, Benveniste J.
    Journal: Br J Pharmacol; 1989 Jun; 97(2):469-74. PubMed ID: 2758225.
    Abstract:
    1. The thienotriazolodiazepine WEB 2086 and the gingkolide BN52021 have been evaluated as antagonists of Paf-acether (Paf) by studying their effects on Paf-induced relaxation and Paf-induced prostaglandin E2 (PGE2) production in histamine-contracted guinea-pig tracheal preparations. 2. Relaxation induced by Paf 4 microM 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. 3. WEB 2086 inhibited in a dose-related manner (IC50 = 21.2 nM) the relaxant effect induced by Paf and, at 1 microM, suppressed Paf-induced release of PGE2. 4. BN 52021 100 microM inhibited to about 60% Paf-induced relaxation of histamine-contracted guinea-pig tracheal preparations, but completely abolished Paf-induced increase in PGE2. 5. Both antagonists had no effects on relaxations induced by arachidonic acid 10 microM or PGE2 0.1-1 microM in histamine-contracted guinea-pig tracheal preparations. 6. 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.
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