Galanin receptor antagonist M35 but not M40 or C7 ameliorates cerulein-induced acute pancreatitis in mice

M. Bhandari, M. Kawamoto, A. C. Thomas, S. G. Barreto, A. C. Schloithe, C. J. Carati, J. Toouli, G. T.P. Saccone

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background/Aims: We compared the galanin antagonists C7, M35, M40 and galantide, for their ability to ameliorate acute pancreatitis (AP). Methods: Galanin antagonists were co-administered with 7 hourly cerulein injections used to induce AP. Plasma amylase and lipase activities were measured as indices of AP, and pancreata were harvested at 12 h for histological examination and estimation of myeloperoxidase (MPO) activity. Results: Treatment with galantide, M35 and C7 ameliorated the AP-induced plasma hyperenzymemia by 40-75%. Administration of M40 did not significantly alter plasma hyperenzymemia. Galantide, M35 and M40 significantly reduced the pancreatic MPO activity by 65-80%, whereas C7 increased MPO activity. Galantide and M35 but not C7 or M40 treatment significantly reduced the AP-induced necrosis score by 30-50% compared to the AP alone group. C7 alone increased plasma lipase activity and the pancreatic necrosis score compared with saline treatment alone, whereas the other antagonists were without effect. Conclusion: Galantide and M35 ameliorated the severity of AP, but M40 and C7 had mixed effects. Complex galanin pathways may be involved in cerulein-induced AP. M35 and galantide are potential therapeutic peptides for the treatment of AP and further evaluation should be considered.

Original languageEnglish
Pages (from-to)682-688
Number of pages7
JournalPancreatology
Volume10
Issue number6
DOIs
Publication statusPublished - Mar 2011

Keywords

  • Acute pancreatitis
  • Galanin
  • Galanin antagonists
  • Peptide therapeutics

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