Eicosanoid

Eicosanoids are a family of bioactive lipids derived from 20-carbon polyunsaturated fatty acids, primarily arachidonic acid, that function as local signaling mediators. The major classes include prostaglandins and thromboxanes (collectively the prostanoids), leukotrienes, prostacyclins, lipoxins, and the epoxyeicosatrienoic acids produced by cytochrome P450 enzymes.

Biosynthesis begins with hydrolysis of membrane phospholipids by phospholipase A2 to release arachidonic acid. Arachidonic acid is then metabolized by cyclooxygenases (COX-1 and COX-2) to prostaglandin H2, a precursor to prostanoids and thromboxanes; or by lipoxygenases (e.g., 5-LOX) to leukotrienes and lipoxins; or by cytochrome P450 epoxygenases to EETs.

Eicosanoids act locally to regulate inflammation, pain and fever, vascular tone, platelet aggregation, bronchial and GI motility, kidney function, and reproductive processes. They exert effects through specific G protein-coupled receptors; different receptor subtypes mediate diverse outcomes (for example, various prostaglandin receptors, TP receptor for thromboxane).

Because of their short half-lives and rapid inactivation, eicosanoids act transiently and are tightly regulated. They are metabolized by specific synthases and inactivating enzymes, and signal termination involves receptor degradation and enzymatic catabolism.

Clinically, nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzymes and reduce prostanoid synthesis, providing analgesic, antipyretic, and anti-inflammatory effects. Aspirin irreversibly inhibits COX-1 in platelets. Leukotriene antagonists and synthesis inhibitors are used in asthma. Prostacyclin analogs and receptor-targeted therapies treat conditions such as pulmonary arterial hypertension and inflammatory diseases; adverse effects include gastric irritation and bronchospasm in susceptible individuals.