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Galanin receptor antagonist m35 but not m40 or c7 ameliorates cerulein-induced acute pancreatitis in mice.

AbstractBACKGROUND/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. and IAP.
AuthorsM Bhandari, M Kawamoto, A C Thomas, S G Barreto, A C Schloithe, C J Carati, J Toouli, G T P Saccone
JournalPancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] (Pancreatology) Vol. 10 Issue 6 Pg. 682-8 ( 2010) ISSN: 1424-3911 [Electronic] Switzerland
PMID21242707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 S. Karger AG, Basel.
Chemical References
  • Complement C7
  • M40
  • Peptide Fragments
  • Receptors, Galanin
  • galanin-(1-13)-bradykinin-(2-9)-amide
  • Galanin
  • Ceruletide
  • Peroxidase
  • Bradykinin
Topics
  • Animals
  • Bradykinin (analogs & derivatives, pharmacology)
  • Ceruletide (toxicity)
  • Complement C7 (pharmacology)
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Galanin (pharmacology)
  • Male
  • Mice
  • Necrosis (chemically induced)
  • Pancreas (drug effects, metabolism, pathology)
  • Pancreatitis, Acute Necrotizing (chemically induced, metabolism, prevention & control)
  • Peptide Fragments (pharmacology)
  • Peroxidase (blood)
  • Receptors, Galanin (antagonists & inhibitors)

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