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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

The Specific Type-4 Phosphodiesterase Inhibitor Mesopram Alleviates Experimental Colitis in Mice

Florian Loher, Kathrin Schmall, Philipp Freytag, Nikola Landauer, Roland Hallwachs, Christian Bauer, Britta Siegmund, Florian Rieder, Hans-Anton Lehr, Marc Dauer, Joachim Friedrich Kapp, Stefan Endres and Andreas Eigler
Journal of Pharmacology and Experimental Therapeutics May 2003, 305 (2) 549-556; DOI: https://doi.org/10.1124/jpet.102.039529
Florian Loher
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Kathrin Schmall
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Philipp Freytag
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Nikola Landauer
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Roland Hallwachs
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Christian Bauer
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Britta Siegmund
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Florian Rieder
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Hans-Anton Lehr
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Marc Dauer
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Joachim Friedrich Kapp
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Stefan Endres
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Andreas Eigler
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Abstract

Mesopram, a specific inhibitor of type-4 phosphodiesterase, decreases the synthesis of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In the present study, we investigated the effect of mesopram in dextran sulfate sodium (DSS)-induced murine colitis. In the preventive model, colitis was induced by DSS simultaneously with the application of mesopram in BALB/c mice. In the therapeutic model, colitis was induced in BALB/c mice by DSS over 7 days. At day 8, DSS was discontinued, and treatment was started. Mesopram was applied intraperitoneally or orally. The clinical score was calculated daily during the course of each study. Post mortem, colon length, histologic score, and expression of TNF-α and IFN-γ in colons were determined. In the preventive model, mesopram significantly reduced the maximal clinical score, decreased colon shortening, and the histologic score. A dose finding study, using the preventive model, showed that most clinical and post mortem benefit was achieved with 50 mg/kg mesopram compared with 2 and 10 mg/kg. In the therapeutic model, i.p. mesopram treatment led to a significant reduction of clinical score. Both, i.p. and p.o. mesopram significantly reversed DSS-induced colon shortening and reduced the ex vivo colonic production of IFN-γ. We conclude that the specific type-4 phosphodiesterase inhibitor mesopram ameliorates murine colitis both in a preventive and a therapeutic setting.

Footnotes

  • This work was supported by Schering AG (Berlin, Germany). These data are part of the dissertation of Kathrin Schmall (Medizinische Klinik Innenstadt of the Ludwig-Maximilians-University, Munich, in preparation).

  • DOI: 10.1124/jpet.102.039529

  • Abbreviations:
    TNF-α
    tumor necrosis factor-α
    INF-γ
    interferon-γ
    PDE
    phosphodiesterase
    DSS
    dextran sulfate sodium
    HEC
    hydroxyethylcellulose
    ELISA
    enzyme-linked immunosorbent assay
    • Received May 28, 2002.
    • Accepted January 24, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 305 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 305, Issue 2
1 May 2003
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

The Specific Type-4 Phosphodiesterase Inhibitor Mesopram Alleviates Experimental Colitis in Mice

Florian Loher, Kathrin Schmall, Philipp Freytag, Nikola Landauer, Roland Hallwachs, Christian Bauer, Britta Siegmund, Florian Rieder, Hans-Anton Lehr, Marc Dauer, Joachim Friedrich Kapp, Stefan Endres and Andreas Eigler
Journal of Pharmacology and Experimental Therapeutics May 1, 2003, 305 (2) 549-556; DOI: https://doi.org/10.1124/jpet.102.039529

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

The Specific Type-4 Phosphodiesterase Inhibitor Mesopram Alleviates Experimental Colitis in Mice

Florian Loher, Kathrin Schmall, Philipp Freytag, Nikola Landauer, Roland Hallwachs, Christian Bauer, Britta Siegmund, Florian Rieder, Hans-Anton Lehr, Marc Dauer, Joachim Friedrich Kapp, Stefan Endres and Andreas Eigler
Journal of Pharmacology and Experimental Therapeutics May 1, 2003, 305 (2) 549-556; DOI: https://doi.org/10.1124/jpet.102.039529
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