Constitutive Cyclooxygenase-2 Expression in Healthy Human and Rabbit Gastric Mucosa

  1. Katja C. Zimmermann1,
  2. Mario Sarbia2,
  3. Karsten Schrör1 and
  4. Artur-Aron Weber1
  1. 1Institut für Pharmakologie (K.C.Z., K.S., A.-A.W.) and2Institut für Pathologie (M.S.), Heinrich-Heine-Universität, Düsseldorf, Germany

    Abstract

    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.

    Footnotes

    • Send reprint requests to: Dr. Karsten Schrör, Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany. E-mail: schroer{at}pharma.uni-duesseldorf.de

    • The study was supported in part by the Forschungsgruppe Herz-Kreislauf e.V. Düsseldorf. The data presented in this article are part of a doctoral thesis.

    • Abbreviations:
      COX
      cyclooxygenase
      PBS
      phosphate-buffered saline
      PG
      prostaglandin
      15-HETE
      15-hydroxyeicosatetraenoic acid
      LPS
      lipopolysaccharide
      PMA
      phorbol-12-myristate-13-acetate
      PCR
      polymerase chain reaction
      RT
      reverse transcription
      • Received April 2, 1998.
      • Accepted June 3, 1998.
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    1. Molecular Pharmacology September 1, 1998 vol. 54 no. 3 536-540
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