CONSTITUTIVE CYCLOOXYGENASE-2 EXPRESSION IN HEALTHY-HUMAN AND RABBIT GASTRIC-MUCOSA

Selective cyclooxygenase (COX)-2 inhibitors are expected to cause fewe r gastric side effects because of sparing of COX-1-dependent prostagla ndin (PG) synthesis in the gastric mucosa. However, the possible contr ibution of COX-2 to overall gastric PG biosynthesis is not known. This study demonstrates constitutive expression of COX-2 mRNA and protein in apparently healthy human and rabbit gastric mucosa. This basal expr ession of COX-2 protein in human gastric mucosa was increased by lipop olysaccharide and phorbol ester, indicating its up-regulation in respo nse to appropriate stimuli. The functional significance of COX-2-depen dent PG formation was studied in terms of PGE(2) generation in the rab bit mucosa and its inhibition by the COX-2-selective inhibitor flosuli de. There was concentration-dependent (IC50 = 107 +/- 55 nM) and ultim ately complete inhibition of PGE(2) generation by flosulide. In additi on, gastric mucosa generated 15-hydroxyeicosatetraenoic acid upon trea tment with acetylsalicylic acid. The data suggest an important role fo r COX-2-dependent PG production in apparently healthy gastric mucosa a nd raise the issue of whether selective COX-2 inhibitors might also in terfere with physiological PG formation and actions in the stomach.