Prostaglandins

Prostaglandins are a group of lipid compounds known as prostanoids that are derived from arachidonic acid and act as local mediators in most tissues. They function as autocrine or paracrine regulators, influencing inflammation, vascular tone, smooth muscle activity, renal function, and reproductive processes. Prostaglandins are rapidly synthesized and inactivated, giving them short-lived, localized effects.

Biosynthesis and classification: Arachidonic acid released from membrane phospholipids by phospholipase A2 is converted by cyclooxygenase enzymes COX-1 and COX-2 into the unstable intermediate prostaglandin G2/H2 (PGH2). PGH2 is then converted by specific synthases into the main prostanoids: PGE2, PGD2, PGF2α, prostacyclin (PGI2), and thromboxane A2 (TXA2). Each prostanoid signals through its own set of G protein–coupled receptors (for example EP1-4 for PGE2, DP for PGD2, FP for PGF2α, IP for PGI2, and TP for TXA2).

Physiological roles: PGE2 and PGI2 promote vasodilation and increase vascular permeability; TXA2 promotes platelet aggregation and vasoconstriction. PGE2 is involved in fever and pain signaling, gastric mucosal protection, and regulation of renal blood flow. PGD2 participates in sleep regulation and inflammatory responses; PGF2α influences smooth muscle contraction. Prostaglandins also regulate ovulation, labor, and the patency of the fetal ductus arteriosus.

Clinical relevance: NSAIDs inhibit COX enzymes and reduce prostaglandin synthesis, providing analgesic and anti-inflammatory effects but potentially causing gastric, renal, and cardiovascular side effects. Therapeutic prostaglandin analogs and antagonists include misoprostol (PGE1 analog) to prevent NSAID ulcers, dinoprostone (PGE2) for labor induction, alprostadil (PGE1) for erectile dysfunction and ductus arteriosus maintenance, and prostacyclin analogs such as epoprostenol, iloprost, and treprostinil for pulmonary arterial hypertension.