Cerulein-induced acute pancreatitis in PACAP knockout mice.
In our previous study, we reported that cerulein-induced acute pancreatitis is aggravated in pancreatic β-cell-specific pituitary adenylate cyclase-activating polypeptide (PACAP) transgenic mice, showing that an increase in pancreatic PACAP is a risk factor for progression of acute pancreatitis. Accordingly, in this study, we examined the progression of cerulein-induced acute pancreatitis in PACAP knockout (KO) mice. Unexpectedly, after cerulein, about 60% of the KO mice showed severe hypothermia below 30°C by 12 h and most of them died within 72 h. In contrast, the remaining KO and wild-type mice showed normothermia with no mortality. Thus, KO mice could be classified into two groups as hypothermic (HT-KO) and normothermic (NT-KO) to cerulein. Only HT-KO mice subsequently showed severe mortality, although both HT-KO and NT-KO mice exhibited similar susceptibility of lungs to cerulein toxicity, comparable to that in wild-type mice. Regarding pancreatitis, HT-KO mice showed ameliorated pancreatic damage without any rise in serum enzyme activities, whereas NT-KO mice exhibited a similar degree of pancreatitis to wild-type mice. Taken together, the present results indicate that lack of pancreatic PACAP did not aggravate, but rather ameliorated, cerulein-induced pancreatitis. In addition, about half of KO mice showed a novel phenotype in which cerulein caused rapid and severe hypothermia, followed by death.
Sakurai
Yusuke
Y
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Shintani
Norihito
N
Arimori
Akihiro
A
Hamagami
Ken-Ichi
K
Higuchi
Naoko
N
Inoue
Hiroaki
H
Ikeda
Kazuya
K
Hayata
Atsuko
A
Hashimoto
Hitoshi
H
Baba
Akemichi
A
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002108:Ceruletide / Q000494:pharmacology*; D007035:Hypothermia; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010195:Pancreatitis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009195:Peroxidase / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D002108:Ceruletide; D009195:Peroxidase