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Inhibition of leukotriene release in anaphylactic guinea‐pig hearts by a 5‐lipoxygenase inhibitor, CGS 8515
Author(s) -
Yaacob H.B.,
Piper Priscilla J.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11771.x
Subject(s) - leukotriene , leukotriene c4 , leukotriene d4 , guinea pig , vasoconstriction , lipoxygenase , pharmacology , thromboxane b2 , leukotriene b4 , chemistry , thromboxane a2 , medicine , biochemistry , enzyme , receptor , platelet , inflammation , asthma
1 Ovalbumen (100μg)‐induced coronary vasoconstriction and decrease in cardiac developed tension were studied in isolated perfused hearts from sensitized guinea‐pigs. Leukotriene‐like material released in the cardiac effluent was assayed against synthetic leukotriene C 4 (LTC 4 ). 2 LTC 4 was released in a time‐dependent fashion, and release was enhanced when hearts were challenged in the presence of indomethacin (2.8 μ m ). The release was maximal at 2–3 min and detectable for as long as 10 min following ovalbumen challenge. Immunoreactive (ir) thromboxane‐B 2 (TxB 2 ) was also detected in cardiac effluent which had been partially purified using C 18 Sep‐Paks. 3 CGS 8515 (0.03–1.0 μ m ), an inhibitor of 5‐lipoxygenase, dose‐dependently inhibited ovalbumen‐induced coronary vasoconstriction and leukotriene‐C 4 release. CGS 8515 inhibited ovalbumen‐induced decreases in cardiac developed tension at 0.3 and 1.0 μ m , but did not antagonize coronary vasoconstriction induced by synthetic LTC 4 . 4 The release of cyclo‐oxygenase products following ovalbumen challenge was not inhibited by CGS 8515, but was markedly inhibited by indomethacin (2.8 μ m ) pretreatment. 5 We conclude that leukotrienes have a major role in guinea‐pig cardiac anaphylaxis, and that CGS 8515 has a cardio‐protective action. The results obtained in these experiments in vitro show that CGS 8515 is a potent and selective 5‐lipoxygenase inhibitor.