Cyclo-oxygenase isoenzymes: physiological and pharmacological role

Abstract

Prostaglandins play important roles in inflammation and the maintenance of normal physiological function of several organ systems. Prostaglandin production requires the conversion of arachidonic acid to the intermediate prostaglandin H2 catalysed by the cyclo-oxygenase (COX) enzyme. There are two isoforms of the COX enzyme, COX-1 and COX-2. These isoforms vary in their distribution and expression but are similar in size, substrate specificity and kinetics. Normal physiological functions are mediated by 'constitutive' COX-1, while the inflammatory response is mediated by 'inducible' COX-2. Current nonsteroidal anti-inflammatory drugs inhibit both enzymes to varying degrees and can cause adverse effects in the gastrointestinal tract, kidney, respiratory system and platelets. Newer, selective COX-2 inhibitors offer real hope for safer anti-inflammatory drugs although their long-term safety and efficacy need to be studied as questions remain unanswered about possible physiological functions of COX-2.