Interference of WEB 2086 and BN 52021 with Paf-induced effects on guinea-pig trachea.
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.
Department of Pharmacology, Univ. Florence, Firenze, Italy.
S
S
Brunelleschi
D
D
Renzi
F
F
Ledda
A
A
Giotti
R
R
Fantozzi
C
C
Brink
J
J
Benveniste
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004224:Diterpenes; D046934:Ginkgolides; D006168:Guinea Pigs; D006633:Histamine Antagonists; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*; D014227:Triazines / Q000494:pharmacology*; D014230:Triazoles
D001381:Azepines; D004224:Diterpenes; D046934:Ginkgolides; D006633:Histamine Antagonists; D007783:Lactones; D010972:Platelet Activating Factor; D014227:Triazines; D014230:Triazoles; C052518:WEB 2086; C045856:ginkgolide B; D015232:Dinoprostone