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. 1988 Aug;94(4):1115–1122. doi: 10.1111/j.1476-5381.1988.tb11629.x

Effects of REV 5901, a 5-lipoxygenase inhibitor and leukotriene antagonist, on pulmonary responses to platelet activating factor in the guinea-pig.

G Anderson 1, M Fennessy 1
PMCID: PMC1854098  PMID: 3145088

Abstract

1. The effects of REV 5901 on the platelet activating factor (Paf)-induced (a) bronchoconstriction, (b) contraction of lung parenchymal strips and (c) increased airways responsiveness to histamine, were assessed in the guinea-pig. REV 5901 is a 5-lipoxygenase inhibitor and competitive peptidoleukotriene antagonist which does not inhibit multiple forms of phosphodiesterase. 2. In urethane/pentobarbitone anaesthetized animals, REV 5901 (10 or 30 mg kg-1, i.v.) substantially inhibited the bronchoconstriction, measured as changes in airways resistance (RL) and dynamic lung compliance (Cdyn), induced by leukotriene D4 (2.5 micrograms kg-1, i.v.) but did not attenuate that induced by Paf (50 ng kg-1, i.v.). 3. Paf contracted the lung parenchymal strip in a concentration-dependent manner. REV 5901 (25 microM) neither altered the magnitude of the contractions nor the tissue sensitivity to Paf. The sustained contraction induced by Paf was not affected when REV 5901 was added after the response had reached a plateau. 4. Contractions of parenchymal strips to Paf (50 nM) were prevented by pretreatment with the competitive Paf antagonists, SRI 63441 and WEB 2086. Also WEB 2086, but not SRI 63441, reversed established Paf-induced contractions and relaxed parenchymal strips from intrinsic tone in the absence of Paf. 5. Paf (20 ng kg-1, i.v.) caused an acute increase in airways responsiveness to histamine (4-12 micrograms kg-1, i.v.) which was attenuated by REV 5901 at 10 mg kg-1, i.v. and abolished by 30 mg kg-1, i.v.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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