Characterization of prostaglandin G/H synthase 1 and 2 in rat, dog, monkey, and human gastrointestinal tracts

Background & Aims: In the gastrointestinal tract, prostaglandins are implicated as important mediators of normal physiological processes. Prostaglandin G/H synthase (PGHS) is the first enzyme leading to the formation of prostaglandins. Two forms exist: the constitutive PGHS-1 and the inducible PGHS-2 isoforms. The purpose of this study was to examine the expression of PGHS-1 and -2 in gastrointestinal tissues. Methods: PGHS-1 and -2 expression and activity were examined in rat, dog, monkey, and human gastrointestinal tracts by immunoblot and biochemical assays. Results: PGHS-1 but not PGHS-2 protein was identified in all gastrointestinal tissues. PGHS-1 protein varied throughout the gastrointestinal tracts; interspecies dif- ferences were also noted. Immunohistochemical studies showed PGHS-1 staining of rat endothelial cells in all gastrointestinal regions; PGHS-2-specific staining was noted in a subset of macrophages in 3 of 22 rats examined. Elevated activity was shown in tissues expressing greater concentrations of PGHS-1 protein. Indomethacin, a nonsteroidal anti-inflammatory drug that inhibits both isoforms, inhibited prostaglandin synthesis, whereas NS-398, a selective PGHS-2 inhibitor, showed little or no inhibition of prostaglandin synthesis in gastrointestinal tissues. Conclusions:These results indicate that prostaglandins produced in normal gastrointestinal tissue and required for normal physiological functioning are derived from the PGHS-1 isoform.