Leukotrienes: possible mediators in bronchial asthma.
Leukotrienes (LTs) are generated from human and guinea-pig lung tissue during antigen challenge. Both human and guinea-pig lung generate LTD4, LTC4, and LTE4 are also formed by human lung and LTB4, by guinea-pig lung. LTC4, LTD4, and LTE4 contract guinea-pig trachea and human bronchus, LTC4 and LTD4 being very much more active than histamine. LTB4 shows some activity but rapidly develops tachyphylaxis. In preparations of guinea-pig lung (perfused lung and parenchymal strips) all LTs cause stimulation of a phospholipase and release of thromboxane A2 (TxA2) and other cyclo-oxygenase products. TxA2 is bronchoconstrictor and augments the LT-induced contractions of guinea-pig parenchyma. Contractions of parenchyma are inhibited by indomethacin, carboxyheptylimidazole or mepacrine. LTs are much less active in contracting parenchymal tissue from human, rat or rabbit and there is no evidence of LT-induced release of TxA2 in these tissues. Since LTC4 and LTD4 cause coronary vasoconstriction in guinea-pig or rat isolated hearts and greyhounds in vivo, LTs generated in lung during antigen challenge may contribute to anaphylactic cardiac depression. LTC4 and LTD4 cause vasoconstriction in guinea-pig skin and constrict guinea-pig pulmonary artery. Recently we have shown that LTs are generated from selected arteries by immunological and non-immunological stimulation. Pulmonary (pig, human, guinea-pig) and coronary arteries (pig) produced the highest concentration of LTD4-like material. The generation of LTs by and their possible actions on the pulmonary circulation may be important in respiratory disease. LTs, B4, C4, D4 cause exudation of plasma (sometimes potentiated by prostaglandins) in the skin of various species. If LTs have similar actions in the lung they may contribute to oedema of the airways. LTC4 is a weak stimulator of mucin secretion in cat trachea but may synergise with prostaglandins released in allergic conditions.
D000818:Animals; D001249:Asthma / Q000209:etiology*; D001980:Bronchi / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology*; D017999:Leukotriene E4; D009077:Mucins / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D013189:SRS-A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
D009077:Mucins; D013189:SRS-A; D007975:Leukotriene B4; D017999:Leukotriene E4