Galanin mediates the pathogenesis of cerulein-induced acute pancreatitis in the mouse

Mayank Bhandari, Anthony Thomas, Damian Hussey, X Li, Surendra Jaya, Charmaine Woods, Ann Schloithe, George Mayne, Colin Carati, James Toouli, Christopher Ormandy, Gino Saccone

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    15 Citations (Scopus)

    Abstract

    Objectives: Acute pancreatitis (AP) is characterized by pancreatic microcirculatory and secretory disturbances. As galanin can modulate pancreatic vascular perfusion, we sought to determine if galanin plays a role in AP. Methods: Acute pancreatitis was induced in wild-type and galanin gene knockout mice by intraperitoneal injections of cerulein. The severity of AP was evaluated (plasma amylase and lipase, myeloperoxidase activity, and acinar cell necrosis) with and without treatment with galanin or the antagonist galantide. Galanin receptor messenger RNA expression in mouse pancreas was measured by reverse transcription-polymerase chain reaction and Western blot analysis. Results: Galantide ameliorated AP, reducing all indices by 25% to 40%, whereas galanin was without effect. In galanin knockout mice, all indices of AP were reduced 25% to 50% compared with wild-type littermates. Galanin administration to the knockout mice exacerbated AP such that it was comparable with the AP induced in the wild-type mice. Conversely, administration of galantide to the galanin knockout mice did not affect the AP, whereas AP was ameliorated in the wild-type mice. The 3 galanin receptor subtypes are expressed in mouse pancreas, with receptor subtype 3 expression predominating. Conclusions: These data implicate a role for galanin in AP and suggest a potential clinical application for galanin antagonists in treatment.

    Original languageEnglish
    Pages (from-to)182-187
    Number of pages6
    JournalPancreas
    Volume39
    Issue number2
    DOIs
    Publication statusPublished - 1 Mar 2010

    Keywords

    • Acute pancreatitis
    • Galanin
    • Galanin receptors
    • Galantide

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