Galanin Receptor Antagonist M35 but Not M40 or C7 Ameliorates Cerulein-Induced Acute Pancreatitis in Mice

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2011-03, Vol.10 (6), p.682-688
• Main Authors: Bhandari, M, Kawamoto, M, Thomas, A.C, Barreto, S.G, Schloithe, A.C, Carati, C.J, Toouli, J, Saccone, G.T.P
• Format: Article
• Language: English
• Subjects: Acute pancreatitis; Animals; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Ceruletide - toxicity; Complement C7 - pharmacology; Disease Models, Animal; Drug Therapy, Combination; Endocrinology & Metabolism; Galanin; Galanin - pharmacology; Galanin antagonists; Gastroenterology and Hepatology; Male; Mice; Necrosis - chemically induced; Original Paper; Pancreas - drug effects; Pancreas - metabolism; Pancreas - pathology; Pancreatitis, Acute Necrotizing - chemically induced; Pancreatitis, Acute Necrotizing - metabolism; Pancreatitis, Acute Necrotizing - prevention & control; Peptide Fragments - pharmacology; Peptide therapeutics; Peroxidase - blood; Receptors, Galanin - antagonists & inhibitors
• ISSN: 1424-3903; 1424-3911
• DOI: 10.1159/000314603

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.