Contractile activities of several cysteine-containing leukotrienes in the guinea-pig lung strip.

Eight biosynthetically formed cysteine-containing leukotrienes dose dependently (0.01-100 nM) contracted parenchymal strips of guinea-pig lung. The response to the leukotrienes was slow in onset, remarkably long-lasting and often tachyphylactic upon repeated administration. All the leukotrienes (LTC3, 8,9-LTC3, LTC4, 11-trans-LTC4, LTC5, LTD4, LTE4 and 11-trans-LTE4) were equally active full agonists for contraction, but approximately 5000 times as potent as histamine on a molar basis. Radiolabelled leukotriene C was insignificantly metabolized during the assay of contractile activity, indicating that the leukotrienes were active per se. The equipotency of LTC4, LTD4 and LTE4 also indicates that each of these three major constituents of slow reacting substance of anaphylaxis (SRS-A), may be considered a significant mediator of allergen-induced bronchoconstriction. In addition, the closely similar contractile activity of glutathionyl-substituted leukotrienes derived from polyunsaturated fatty acids other than arachidonic acid, suggests that they may contribute to bronchospastic disease under pathological and nutritional conditions promoting their formation.