Pharmacological Interference in Arachidonic Acid Cascade
In order to be metabolized by oxidative tissue enzymes arachidonic acid (AA) has to be liberated from the cellular phospholipids by phospholipase A2 (1). In certain cells, e.g. in platelets, phospholipase requires calcium ions for its optimal biochemical activity (2), and therefore Ca2+ ionophors activate AA cascade (3) while the drugs which rise intracellular cAMP levels sequestrate Ca2+, and thus inhibit AA liberation and its subsequent metabolism (4). Mepacrine and bromophenacetyl bromide are direct inhibitors of phospholipase A2 (5). We have proposed (6,7) that the liberation of AA from intact tissues is hindered by glucocorticosteroids as well as by anti-inflammatory steroids, eg. dexymethasone. Other authors since have confirmed our hypothesis (8,9,10), and Flower and Blackwell (11) demonstrated that glucocorticosteroids induce the endogenous synthesis of a phospholipase A2 inhibitor.
KeywordsPlatelet Aggregation Human Platelet Dienoic Acid Prostaglandin Biosynthesis Arachidonic Acid Cascade
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