CYCLOOXYGENASE-1 AND CYCLOOXYGENASE-2

Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is th e key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a secon d gene with COX activity and called it COX-2. However, COX-2 was induc ible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and co ntrol of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor se lectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In additi on to the induction of COX-2 in inflammatory lesions, it is present co nstitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are also important in ovulation and in the birth process. The d iscovery of COX-2 has made possible the design of drugs that reduce in flammation without removing the protective PGs in the stomach and kidn ey made by COX-1. These highly selective COX-2 inhibitors may not only be anti-inflammatory but may also be active in colon cancer and Alzhe imer's disease.