Galanin mediates the pathogenesis of cerulein-induced acute pancreatitis in the mouse.
OBJECTIVE
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.
Bhandari
Mayank
M
Department of General and Digestive Surgery, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
Thomas
Anthony C
AC
Hussey
Damian J
DJ
Li
Xin
X
Jaya
Surendra P
SP
Woods
Charmaine M
CM
Schloithe
Ann C
AC
Mayne
George C
GC
Carati
Colin J
CJ
Toouli
James
J
Ormandy
Christopher J
CJ
Saccone
Gino T P
GT
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D004195:Disease Models, Animal; D005260:Female; D019004:Galanin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D012333:RNA, Messenger / Q000378:metabolism; D044088:Receptors, Galanin / Q000378:metabolism; D012720:Severity of Illness Index; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D012333:RNA, Messenger; D044088:Receptors, Galanin; C074975:galantide; D013373:Substance P; D019004:Galanin; D002108:Ceruletide