MITOGEN-INDUCIBLE PROSTAGLANDIN G/H SYNTHASE - A NEW TARGET FOR NONSTEROIDAL ANTIINFLAMMATORY DRUGS

Prostaglandins have been shown to be involved in many different biological processes, under both normal and pathological conditions. As the key enzyme in the production of prostaglandins and thromboxanes, prostaglandin G/H synthase (PGHS) has been well characterized, including extensive studies as a pharmacological target of the nonsteroidal antiinflammatory drugs (NSAIDs). The gene for this enzyme has been cloned, sequenced, and characterized from sheep, mouse, and human sources. Recently, a new form of this enzyme, a mitogen-inducible PGHS (miPGHS), was identified. Comparisons between these two genes and their protein products have identified significant differences, including structural differences in the proteins and their mRNAs. The genes encoding these two isoenzymes are not coordinately regulated in cultured cells or in tissues. The discovery of this second form of PGHS may change our understanding of how NSAIDs exert their effects. miPGHS is believed to be a new, unique target of NSAIDs which could have a different sensitivity to many of these drugs, compared to the previously identified PGHS.