TY - JOUR
T1 - Interference of WEB 2086 and BN 52021 with Paf-induced effects on guinea-pig trachea
AU - Brunelleschi, S.
AU - Renzi, D.
AU - Ledda, F.
AU - Giotti, A.
AU - Fantozzi, R.
AU - Brink, C.
AU - Benveniste, J.
PY - 1989
Y1 - 1989
N2 - 1. The thienotriazolodiazepine WEB 2086 and the gingkolide BN 52021 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 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. 3. 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. 4. 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. 5. 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. 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.
AB - 1. The thienotriazolodiazepine WEB 2086 and the gingkolide BN 52021 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 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. 3. 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. 4. 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. 5. 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. 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.
UR - http://www.scopus.com/inward/record.url?scp=0024322352&partnerID=8YFLogxK
U2 - 10.1111/j.1476-5381.1989.tb11974.x
DO - 10.1111/j.1476-5381.1989.tb11974.x
M3 - Article
SN - 0007-1188
VL - 97
SP - 469
EP - 474
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 2
ER -