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. 1988 Jul;26(1):65–72. doi: 10.1111/j.1365-2125.1988.tb03365.x

Effect of a PAF antagonist, BN52063, on PAF-induced bronchoconstriction in normal subjects.

N M Roberts 1, M McCusker 1, K F Chung 1, P J Barnes 1
PMCID: PMC1386501  PMID: 3203062

Abstract

1. The effects of an oral platelet activating factor (PAF) antagonist, BN52063, or matched placebo on inhaled PAF challenge were assessed in a double-blind study in eight normal subjects. 2. PAF (24 micrograms) induced an immediate bronchoconstriction, with a maximum fall in flow at 30% of vital capacity from a partial flow volume manoeuvre (Vp30) of 47.1 +/- 7% (mean +/- s.e. mean) 5 min after inhalation following placebo treatment. Repeated PAF challenges at 15 min intervals resulted in tachyphylaxis of the bronchoconstrictor response. 3. Two hours after the ingestion of BN52063 (120 mg) the maximum bronchoconstriction induced by inhaled PAF was attenuated (35.9 +/- 9% fall at 5 min) with a significant reduction (P less than 0.05) in response after the first and second inhalations. 4. Inhaled PAF induced an immediate neutropenia (73.2 +/- 9% fall 5 min after inhalation) followed by a rebound neutrophilia, which were unaffected by pretreatment with BN52063. 5. Oral ingestion of a dose of BN52063 which is effective in reducing skin responses to PAF gave partial protection against the bronchoconstrictor effect of inhaled PAF in normal subjects.

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Selected References

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  1. Archer C. B., Page C. P., Morley J., MacDonald D. M. Accumulation of inflammatory cells in response to intracutaneous platelet activating factor (Paf-acether) in man. Br J Dermatol. 1985 Mar;112(3):285–290. doi: 10.1111/j.1365-2133.1985.tb04855.x. [DOI] [PubMed] [Google Scholar]
  2. Archer C. B., Page C. P., Paul W., Morley J., MacDonald D. M. Inflammatory characteristics of platelet activating factor (PAF-acether) in human skin. Br J Dermatol. 1984 Jan;110(1):45–50. doi: 10.1111/j.1365-2133.1984.tb07310.x. [DOI] [PubMed] [Google Scholar]
  3. Barnes P. J., Gribbin H. R., Osmanliev D., Pride N. B. Partial flow-volume curves to measure bronchodilator dos-response curves in normal humans. J Appl Physiol Respir Environ Exerc Physiol. 1981 Jun;50(6):1193–1197. doi: 10.1152/jappl.1981.50.6.1193. [DOI] [PubMed] [Google Scholar]
  4. Bouhuys A., Hunt V. R., Kim B. M., Zapletal A. Maximum expiratory flow rates in induced bronchoconstriction in man. J Clin Invest. 1969 Jun;48(6):1159–1168. doi: 10.1172/JCI106073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Braquet P., Touqui L., Shen T. Y., Vargaftig B. B. Perspectives in platelet-activating factor research. Pharmacol Rev. 1987 Jun;39(2):97–145. [PubMed] [Google Scholar]
  6. Camussi G., Pawlowski I., Tetta C., Roffinello C., Alberton M., Brentjens J., Andres G. Acute lung inflammation induced in the rabbit by local instillation of 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine or of native platelet-activating factor. Am J Pathol. 1983 Jul;112(1):78–88. [PMC free article] [PubMed] [Google Scholar]
  7. Camussi G., Tetta C., Bussolino F., Caligaris Cappio F., Coda R., Masera C., Segoloni G. Mediators of immune-complex-induced aggregation of polymorphonuclear neutrophils. II. Platelet-activating factor as the effector substance of immune-induced aggregation. Int Arch Allergy Appl Immunol. 1981;64(1):25–41. doi: 10.1159/000232671. [DOI] [PubMed] [Google Scholar]
  8. Chesney C. M., Pifer D. D., Huch K. M. Desensitization of human platelets by platelet activating factor. Biochem Biophys Res Commun. 1985 Feb 28;127(1):24–30. doi: 10.1016/s0006-291x(85)80120-0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Czarnetzki B. M., Benveniste J. Effect of synthetic PAF-acether on human neutrophil function. Agents Actions. 1981 Dec;11(6-7):549–550. doi: 10.1007/BF01978734. [DOI] [PubMed] [Google Scholar]
  11. Demopoulos C. A., Tsabikakis G. E., Kapoulas V. M. Intravascular pathobiology of acetyl glyceryl ether phosphorylcholine (AGEPC), a synthetic platelet-activating factor (PAF). I. Intravenous infusion in guinea pigs. Immunol Lett. 1981 Aug;3(3):133–135. [PubMed] [Google Scholar]
  12. Denjean A., Arnoux B., Benveniste J., Lockhart A., Masse R. Bronchoconstriction induced by intratracheal administration of platelet-activating factor (PAF-acether) in baboons. Agents Actions. 1981 Dec;11(6-7):567–568. doi: 10.1007/BF01978743. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Guinot P., Braquet P., Duchier J., Cournot A. Inhibition of PAF-acether induced weal and flare reaction in man by a specific PAF antagonist. Prostaglandins. 1986 Jul;32(1):160–163. doi: 10.1016/0090-6980(86)90161-9. [DOI] [PubMed] [Google Scholar]
  15. Halonen M., Palmer J. D., Lohman I. C., McManus L. M., Pinckard R. N. Differential effects of platelet depletion on the physiologic alterations of IgE anaphylaxis and acetyl glyceryl ether phosphorylcholine infusion in the rabbit. Am Rev Respir Dis. 1981 Oct;124(4):416–421. doi: 10.1164/arrd.1981.124.4.416. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Holian O., Ruiz C., Bombeck C. T., Nyhus L. M. Action of histamine and 3-isobutyl-1-methylxanthine on cAMP activation of protein kinase in dog gastric mucosa. Agents Actions. 1983 Feb;13(1):5–9. doi: 10.1007/BF01994274. [DOI] [PubMed] [Google Scholar]
  18. Ingraham L. M., Coates T. D., Allen J. M., Higgins C. P., Baehner R. L., Boxer L. A. Metabolic, membrane, and functional responses of human polymorphonuclear leukocytes to platelet-activating factor. Blood. 1982 Jun;59(6):1259–1266. [PubMed] [Google Scholar]
  19. Keraly C. L., Benveniste J. Specific desensitization of rabbit platelets by platelet-activating factor (PAF-acether) and derivatives. Br J Haematol. 1982 Jun;51(2):313–322. [PubMed] [Google Scholar]
  20. Lefort J., Rotilio D., Vargaftig B. B. The platelet-independent release of thromboxane A2 by Paf-acether from guinea-pig lungs involves mechanisms distinct from those for leukotriene. Br J Pharmacol. 1984 Jul;82(3):565–575. doi: 10.1111/j.1476-5381.1984.tb10795.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lellouch-Tubiana A., Lefort J., Pirotzky E., Vargaftig B. B., Pfister A. Ultrastructural evidence for extravascular platelet recruitment in the lung upon intravenous injection of platelet-activating factor (PAF-acether) to guinea-pigs. Br J Exp Pathol. 1985 Jun;66(3):345–355. [PMC free article] [PubMed] [Google Scholar]
  22. Michoud M. C., Ghezzo H., Amyot R. A comparison of pulmonary function tests used for bronchial challenges. Bull Eur Physiopathol Respir. 1982 Jul-Aug;18(4):609–621. [PubMed] [Google Scholar]
  23. O'Flaherty J. T., Lees C. J., Miller C. H., McCall C. E., Lewis J. C., Love S. H., Wykle R. L. Selective desensitization of neutrophils: further studies with 1-O-alkyl-sn-glycero-3-phosphocholine analogues. J Immunol. 1981 Aug;127(2):731–737. [PubMed] [Google Scholar]
  24. Vargaftig B. B., Lefort J., Chignard M., Benveniste J. Platelet-activating factor induces a platelet-dependent bronchoconstriction unrelated to the formation of prostaglandin derivatives. Eur J Pharmacol. 1980 Jul 25;65(2-3):185–192. doi: 10.1016/0014-2999(80)90391-x. [DOI] [PubMed] [Google Scholar]
  25. 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]

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