Abstract
1. The triazolodiazepine WEB 2086 has been evaluated as an antagonist of platelet-activating factor (Paf) by studying its effects on Paf-induced human platelet aggregation and microvascular leakage in guinea-pigs. 2. WEB 2086 inhibited Paf-induced platelet aggregation in platelet-rich plasma in vitro (IC50 = 117 +/- 35 nM, mean +/- s.d.) but had no effect on adenosine 3',5'-diphosphate-induced aggregation. 3. Paf-induced microvascular leakage, measured by the extravasation of intravenously-injected Evans blue dye, was inhibited in a dose-related fashion in the airways and other tissues by WEB 2086, achieving a maximal inhibitory effect at 10 micrograms kg-1, i.v. 4. However, WEB 2086 (10 micrograms kg-1, i.v.) did not inhibit a comparable increase in vascular permeability induced by ovalbumin in sensitized guinea-pigs. 5. We conclude that WEB 2086 is a potent antagonist of Paf and that Paf does not appear to be responsible for antigen-induced microvascular leakage.
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andersson P. Antigen-induced bronchial anaphylaxis in actively sensitized guinea-pigs. Pattern of response in relation to immunization regimen. Allergy. 1980 Jan;35(1):65–71. doi: 10.1111/j.1398-9995.1980.tb01718.x. [DOI] [PubMed] [Google Scholar]
- Bessin P., Bonnet J., Apffel D., Soulard C., Desgroux L., Pelas I., Benveniste J. Acute circulatory collapse caused by platelet-activating factor (PAF-acether) in dogs. Eur J Pharmacol. 1983 Jan 21;86(3-4):403–413. doi: 10.1016/0014-2999(83)90190-5. [DOI] [PubMed] [Google Scholar]
- Braquet P., Etienne A., Touvay C., Bourgain R. H., Lefort J., Vargaftig B. B. Involvement of platelet activating factor in respiratory anaphylaxis, demonstrated by PAF-acether inhibitor BN 52021. Lancet. 1985 Jun 29;1(8444):1501–1501. doi: 10.1016/s0140-6736(85)92269-x. [DOI] [PubMed] [Google Scholar]
- Casals-Stenzel J., Muacevic G., Weber K. H. Pharmacological actions of WEB 2086, a new specific antagonist of platelet activating factor. J Pharmacol Exp Ther. 1987 Jun;241(3):974–981. [PubMed] [Google Scholar]
- Chung K. F., Aizawa H., Leikauf G. D., Ueki I. F., Evans T. W., Nadel J. A. Airway hyperresponsiveness induced by platelet-activating factor: role of thromboxane generation. J Pharmacol Exp Ther. 1986 Mar;236(3):580–584. [PubMed] [Google Scholar]
- Chung K. F., Dent G., McCusker M., Guinot P., Page C. P., Barnes P. J. Effect of a ginkgolide mixture (BN 52063) in antagonising skin and platelet responses to platelet activating factor in man. Lancet. 1987 Jan 31;1(8527):248–251. doi: 10.1016/s0140-6736(87)90066-3. [DOI] [PubMed] [Google Scholar]
- Cuss F. M., Dixon C. M., Barnes P. J. Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man. Lancet. 1986 Jul 26;2(8500):189–192. doi: 10.1016/s0140-6736(86)92489-x. [DOI] [PubMed] [Google Scholar]
- Evans T. W., Chung K. F., Rogers D. F., Barnes P. J. Effect of platelet-activating factor on airway vascular permeability: possible mechanisms. J Appl Physiol (1985) 1987 Aug;63(2):479–484. doi: 10.1152/jappl.1987.63.2.479. [DOI] [PubMed] [Google Scholar]
- Henocq E., Vargaftig B. B. Accumulation of eosinophils in response to intracutaneous PAF-acether and allergens in man. Lancet. 1986 Jun 14;1(8494):1378–1379. doi: 10.1016/s0140-6736(86)91683-1. [DOI] [PubMed] [Google Scholar]
- Humphrey D. M., McManus L. M., Satouchi K., Hanahan D. J., Pinckard R. N. Vasoactive properties of acetyl glyceryl ether phosphorylcholine and analogues. Lab Invest. 1982 Apr;46(4):422–427. [PubMed] [Google Scholar]
- Lambrecht G., Parnham M. J. Kadsurenone distinguishes between different platelet activating factor receptor subtypes on macrophages and polymorphonuclear leucocytes. Br J Pharmacol. 1986 Feb;87(2):287–289. doi: 10.1111/j.1476-5381.1986.tb10816.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morley J., Page C. P., Paul W. Inflammatory actions of platelet activating factor (Pafacether) in guinea-pig skin. Br J Pharmacol. 1983 Nov;80(3):503–509. doi: 10.1111/j.1476-5381.1983.tb10722.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Donnell S. R., Barnett C. J. Microvascular leakage to platelet activating factor in guinea-pig trachea and bronchi. Eur J Pharmacol. 1987 Jun 26;138(3):385–396. doi: 10.1016/0014-2999(87)90477-8. [DOI] [PubMed] [Google Scholar]
- Saria A., Lundberg J. M. Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues. J Neurosci Methods. 1983 May;8(1):41–49. doi: 10.1016/0165-0270(83)90050-x. [DOI] [PubMed] [Google Scholar]
- Sánchez-Crespo M., Fernández-Gallardo S., Nieto M. L., Baranès J., Braquet P. Inhibition of the vascular actions of IgG aggregates by BN 52021, a highly specific antagonist of paf-acether. Immunopharmacology. 1985 Oct;10(2):69–75. doi: 10.1016/0162-3109(85)90031-1. [DOI] [PubMed] [Google Scholar]
- Touvay C., Etienne A., Braquet P. Inhibition of antigen-induced lung anaphylaxis in the guinea-pig by BN 52021 a new specific paf-acether receptor antagonist isolated from Ginkgo biloba. Agents Actions. 1986 Jan;17(3-4):371–372. doi: 10.1007/BF01982650. [DOI] [PubMed] [Google Scholar]
- Udaka K., Takeuchi Y., Movat H. Z. Simple method for quantitation of enhanced vascular permeability. Proc Soc Exp Biol Med. 1970 Apr;133(4):1384–1387. doi: 10.3181/00379727-133-34695. [DOI] [PubMed] [Google Scholar]
- Wardlaw A. J., Moqbel R., Cromwell O., Kay A. B. Platelet-activating factor. A potent chemotactic and chemokinetic factor for human eosinophils. J Clin Invest. 1986 Dec;78(6):1701–1706. doi: 10.1172/JCI112765. [DOI] [PMC free article] [PubMed] [Google Scholar]