Which of the following statements about the leukotrienes LTC4, LTD4, and LTE4 is most correct?
ExplanationThe leukotrienes LTC4 , LTD4 , and LTE4 are 5’-lipoxygenase metabolites of arachidonic acid. When lung tissue is challenged with antigen in sensitive individuals, LTC4 is formed and subsequently metabolized to LTD4 and LTE4 . These leukotrienes are not stored but produce bronchoconstriction, increased capillary permeability, and increased mucus formation for an extended time because of their slow tissue clearance. Because the first enzyme in synthesis of leukotrienes from arachidonic acid is 5’- lipoxygenase rather than COX, aspirin (choice A) does not inhibit their biosynthesis. Another leukotriene, LTB4 , is a potent chemotactic agent for polymorphonuclear leukocytes (choice B), but the cysteine-linked leukotrienes LTC4 , LTD4 , and LTE4 do not share this property. Platelets do not contain 5’-lipoxygenase (although they do contain 12’-lipoxygenase), and leukotrienes are not stored in platelet granules (choice D). The COX product of arachidonic acid, TXA2 , is critical in platelet physiology, and acetylation of COX by aspirin accounts for the effect of this drug in inhibiting platelet function. The leukotrienes possess significant cardiovascular effects (choice E); they produce hypotension by decreasing intravascular volume and reducing cardiac contractility by constricting coronary vessels, thus reducing coronary blood flow.
