The action of leukotriene B4 (LTB4) on the lung

The actions of leukotriene B4 (LTB4), 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 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. LTB4 is three times more potent than histamine (molar concentration) to contract the parenchymal strips and the contraction to LTB4 as well as to SRS-A lasted longer. The contraction to LTB4 is blocked by indomethacin (20 micrograms/ml), reduced by polyphloretin phosphate (50 micrograms/ml) and unaffected by FPL-55712 (1 micrograms/ml). Following its injection in the pulmonary artery of a perfused lung, LTB4 (1 microgram) induced the release of RCS (Rabbit Aorta Contracting Substance: a mixture of prostaglandins and thromboxanes) which can be abolished by indomethacin (1 microgram/ml). These findings suggest (a) that in the lung, LTB4 is a myotropic agent three times more powerful than histamine (b) that LTB4 stimulated a receptor which is different of histamine of SRS-A receptors, and (c) that its contractile action in the lung is mediated by prostaglandins and thromboxanes.