Bronchial hyperresponsiveness to contractile agonists and nonspecific irritants is a characteristic feature of bronchial asthma. The mechanisms causing this hyperirritability are unknown. The existence of separate receptors for leukotrienes C4 and D4 (LTCC4 and LTD4) has been, demonstrated previously by physiologic and radioligand binding studies. The rank order of potency of the sulfidopeptide leukotrienes for contracting tracheal spirals [leukotrwiene E4 (LTE4) > LID4 = LTC4J is different from that for contracting parenchymal strips (LTD4> LTE4> LTC4), thereby suggesting the existence of a separate receptor for LTE4. We now report that 'LTE4, the most stable of the leukotrienes comprising slow reacting substance of anaphylaxis, enhances the contractile response of guinea pig tracheal spirals but not of parenchymal strips, to histamine in a time-and dose-dependent fashion., The ability of LTE4 to increase histamine responsiveness occurred after removal of the free agonist and recovery of the tissues to baseline tensions and was not produced by lemkotrienes C4 and Lr4, which elicited the same magnitude of contraction of tracheal smooth muscle as LTE4. These findings suggest that LTE4-induced airway hyperirritability is not mediated by the contractile response per se and may be modiated through a receptor distinct from those for leukotrienes C4 and D4.

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