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Vol. 54, Issue 3, 536-540, September 1998
Institut für Pharmakologie (K.C.Z., K.S., A.-A.W.) and
Institut für Pathologie (M.S.), Heinrich-Heine-Universität,
Düsseldorf, Germany
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 PGE2
generation 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.
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