Abstract
The actions of leukotriene B 4 (LTB 4), a member of a newly discovered pathway of metabolism of arachidonic acid, were investigated both on the guinea-pig perfused lung preparation and on the parenchymal strip and compared to histamine and Slow Reacting Substance of Anaphylaxis (SRS-A). LTB 4 was prepared from human polymorphonuclear leukocytes, extracted and purified by chromatography (Silicic acid and HPLC) and its purity was determined by gas chromatography and mass spectrometry. LTB 4 is three times more potent than histamine (molar concentration) to contract the parenchymal strips and the contraction to LTB 4 as well as to SRS-A lasted longer. The contraction to LTB 4 is blocked by indomethacin (20 μg/ml), reduced by polyphloretin phosphate (50 μg/ml) and unaffected by FPL-55712 (1 μg/ml). Following its injection in the pulmonary artery of a perfused lung, LTB 4 (1 μg) induced the release of RCS (Rabbit Aorta Contracting Substance:a mixture of prostaglandins and thromboxanes) which can be abolished by indomethacin (1 μg/ml). These findings suggest (a) that in the lung, LTB 4 is a myotropic agent three times more powerful than histamine (b) that LTB 4 stimulated a receptor which is different of histamine or SRS-A receptors, and (c) that its contractile action in the lung is mediated by prostaglandins and thromboxanes.
Published Version
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