Characterization of Prostaglandin G/H Synthase 1 and 2 in rat, dog, monkey, and human gastrointestinal tracts.
OBJECTIVE
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 differences 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.
Kargman
S
S
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Quebec, Canada.
Charleson
S
S
Cartwright
M
M
Frank
J
J
Riendeau
D
D
Mancini
J
J
Evans
J
J
O'Neill
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004064:Digestive System / Q000187:drug effects / Q000201:enzymology*; D004285:Dogs; D004727:Endothelium / Q000201:enzymology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008253:Macaca mulatta; D008264:Macrophages / Q000201:enzymology; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008969:Molecular Sequence Data; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D012453:Saimiri; D013449:Sulfonamides / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin