RT Book, Section A1 Ricciotti, Emanuela A1 Grosser, Tilo A1 FitzGerald, Garret A. A2 Brunton, Laurence L. A2 Knollmann, Björn C. SR Print(0) ID 1194859593 T1 Lipid-Derived Autacoids: Eicosanoids and Platelet-Activating Factor T2 Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th Edition YR 2023 FD 2023 PB McGraw-Hill Education PP New York, NY SN 9781264258079 LK accessmedicine.mhmedical.com/content.aspx?aid=1194859593 RD 2024/03/29 AB Membrane lipids supply the substrate for the synthesis of eicosanoids and platelet-activating factor (PAF). Arachidonic acid (AA) metabolites, including PGs (prostaglandins), PGI2 (prostacyclin), TxA2 (thromboxane A2), LTs (leukotrienes), and epoxygenase products of cytochromes P450 (CYP)s, collectively the eicosanoids, are not stored but are produced by most cells when a variety of physical, chemical, and hormonal stimuli activate acyl hydrolases that make arachidonate available for further metabolism. Membrane glycerophosphocholine derivatives can be modified enzymatically to produce PAF. PAF is formed by a smaller number of cell types, principally leukocytes, platelets, and endothelial cells. Eicosanoids and PAF lipids function as signaling molecules in many biological processes, including the regulation of vascular tone, renal function, hemostasis, parturition, gastrointestinal (GI) mucosal integrity, and stem cell function. They are also important mediators of innate immunity and inflammation. Several classes of drugs, most notably NSAIDs (nonsteroidal anti-inflammatory drugs) (see Chapter 42), including aspirin, owe their principal therapeutic effects—relief of inflammatory pain and antipyresis—to blockade of PG formation.