The Role of Phospholipase A2 Activating Protein (PLAP) in Regulating Prostanoid Production in Smooth Muscle and Endothelial Cells Following Leukotriene D4 Treatment
Leukotrienes are a family of compounds originally termed the slow-reacting substances of anaphylaxis and are recognized as important mediators of anaphylaxis (1). In particular, leukotriene C4 (LTC4 ) and leukotriene D4 (LTD4) are potent spasmogens in a variety of smooth muscle tissues including trachea, lung, ileum and the vasculature (2.4). The mechanism by which contraction is induced by the leukotrienes (LTs) is not yet known. However, in some experimental systems, but not all, a cyclooxygenase product of arachidonic acid metabolism, possibly thromboxane B2 (TxB2 ), may be involved in mediating leukotrieneinduced effects (3,4). This is based on the observation that inhibitors of cyclooxygenase, such as indomethacin and meclofenamic acid, can block leukotriene-induced contraction of the lung parenchyma, vasculature and the ileum (2.4). In other tissues, most notably guinea pig trachea, the cyclooxygenase products appear to be relatively unimportant mediators of leukotriene effects (5). Furthermore, in the tissues in which cyclooxygenase products appear to be important, thromboxane synthesis may be crucial for the leukotriene responses (4). Although TxB2 is usually assumed to be of platelet origin, the cellular source of LT-induced thromboxane synthesis is not known.
KeywordsArachidonic Acid Phospholipase Activity Cyclooxygenase Product Prostacyclin Synthesis PROSTANOID Production
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