Enzymatic Pathway of Prostaglandin (PG) Formation from Arachidonic Acid and Physiological and Pathological Functions of Cyclooxygenase (COX)-1 and COX-2.

Arachidonic acid is released from membrane phospholipids by phospholipase A2, which is activated by various stimuli (inflammatory, physical, chemical, and mitogenic). Cyclooxygenase-1 is constitutively expressed in tissues and produces prostaglandins which are involved in physiological processes. For example, prostacyclin made by the stomach mucosa protects it from damage by gastric acid, thromboxane A2 (TxA2) made by platelets promotes the clotting of blood when required, and PGE2 made in kidney cells is involved in kidney function. Cyclooxygenase-2 is inducibly expressed, but some constitutive COX-2 is also expressed, particularly in the brain. Cyclooxygenase-2 is mainly induced in inflammation and by mitogens and growth factors. It is induced in macrophages and other inflammatory cells by bacterial lipopolysaccharide and cytokines. It forms mainly PGE2, which with other inflammatory mediators causes pain and fever.