Cyclooxygenase isoenzymes and newer therapeutic potential for selective COX-2 inhibitors

Cyclooxygenase (COX), also known as prostaglandin G/H synthase, is a membra ne-bound enzyme responsible for the oxidation of arachidonic acid to prosta glandins that was first identified over 20 years ago. In the past decade, h owever,more progress has been made in understanding the role of cyclooxygen ase enzymes in various pathophysiological conditions. Two cyclooxygenase is oforms have been identified and are referred to as COX-1 and COX-2. COX-1 e nzyme is constitutively expressed and regulates a number of housekeeping fu nctions such as vascular hemostasis and gastroprotection, whereas COX-2 is inducible (i.e. sites of inflammation) by number of mediators such as growt h factors, cytokines and endotoxins. Nonsteroidal antiinflammatory drugs (N SAIDs) produce their therapeutic effects through inhibition of COX, the enz yme that makes prostaglandins. Nonselective inhibition of COX isoenzyme lea ds to not only beneficia therapeutic effects but also a number of detriment al effects. Beneficial effects are due to inhibition of COX-2 and detriment al effects are due to inhibition of physiological COX-1. The present review discusses the biology as well as the role of these COX isoenzyme sin vario us pathophysiological conditions. (C) 2000 Prous Science. All rights reserv ed.