PT  - JOURNAL ARTICLE
AU  - Katja C. Zimmermann
AU  - Mario Sarbia
AU  - Karsten Schrör
AU  - Artur-Aron Weber
TI  - Constitutive Cyclooxygenase-2 Expression in Healthy Human and Rabbit Gastric Mucosa
AID  - 10.1124/mol.54.3.536
DP  - 1998 Sep 01
TA  - Molecular Pharmacology
PG  - 536--540
VI  - 54
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/54/3/536.short
4100  - http://molpharm.aspetjournals.org/content/54/3/536.full
SO  - Mol Pharmacol1998 Sep 01; 54
AB  - Selective cyclooxygenase (COX)-2 inhibitors are expected to cause fewer gastric side effects because of sparing of COX-1-dependent prostaglandin (PG) synthesis in the gastric mucosa. However, the possible contribution 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 expression of COX-2 protein in human gastric mucosa was increased by lipopolysaccharide and phorbol ester, indicating its up-regulation in response to appropriate stimuli. The functional significance of COX-2-dependent PG formation was studied in terms of PGE2 generation in the rabbit mucosa and its inhibition by the COX-2-selective inhibitor flosulide. There was concentration-dependent (IC50 = 107 ± 55 nm) and ultimately complete inhibition of PGE2generation by flosulide. In addition, gastric mucosa generated 15-hydroxyeicosatetraenoic acid upon treatment with acetylsalicylic acid. The data suggest an important role for COX-2-dependent PG production in apparently healthy gastric mucosa and raise the issue of whether selective COX-2 inhibitors might also interfere with physiological PG formation and actions in the stomach.