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


CONCLUSIONS
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.
Departments of General and Digestive Surgery, Flinders Medical Centre, Flinders University, Adelaide, S.A., Australia.
M
M
Bhandari
M
M
Kawamoto
A C
AC
Thomas
S G
SG
Barreto
A C
AC
Schloithe
C J
CJ
Carati
J
J
Toouli
G T P
GT
Saccone
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002108:Ceruletide / Q000633:toxicity*; D003184:Complement C7 / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D019004:Galanin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009336:Necrosis / Q000139:chemically induced; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D010446:Peptide Fragments / Q000494:pharmacology*; D009195:Peroxidase / Q000097:blood; D044088:Receptors, Galanin / Q000037:antagonists & inhibitors*
D003184:Complement C7; C079517:M40; D010446:Peptide Fragments; D044088:Receptors, Galanin; C074069:galanin-(1-13)-bradykinin-(2-9)-amide; D019004:Galanin; D002108:Ceruletide; D009195:Peroxidase; D001920:Bradykinin