Cyclo-oxygenase isoenzymes: physiological and pharmacological role

Prostaglandins play important roles in inflammation and the maintenance of normal physiological function of several organ systems. Prostaglandin produ ction requires the conversion of arachidonic acid to the intermediate prost aglandin Hz catalysed by the cyclo-oxygenase (COX) enzyme. There are two is oforms of the COX enzyme, COX-I and COX-2. These isoforms vary in their dis tribution and expression but are similar in size, substrate specificity and kinetics. Normal physiological functions are mediated by 'constitutive' CO X-1, while the inflammatory reponse is mediated by 'inducible' COX-2. Curre nt nonsteroidal anti-inflammatory drugs inhibit both enzymes to varying deg rees and can cause adverse effects in the gastrointestinal tract, kidney, r espiratory system and platelets. Newer, selective COX-2 inhibitors offer re al hope for safer anti-inflammatory drugs although their long-term safety a nd efficacy need to be studied as questions remain unanswered about possibl e physiological functions of COX-2.