title: Adenosine uptake inhibition ameliorates cerulein-induced acute pancreatitis in mice.
abstract: OBJECTIVE
  Adenosine shows protective effects against cellular damage and dysfunction under several adverse conditions such as inflammation and ischemia. In the current study, we examined the effects of 3-[1-(6,7-diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1,3 )-quinazolinedione hydrochloride (KF24345), an adenosine uptake inhibitor, on cerulein-induced acute pancreatitis in mice to investigate whether inhibition of adenosine uptake could ameliorate the severity of acute pancreatitis.
  
  
  METHODS
  Acute pancreatitis was induced in mice with six intraperitoneal injections of cerulein (50 microg/kg each) at hourly intervals.
  
  
  RESULTS
  The cerulein injection increased activities of serum amylase and lipase and caused pathologic changes such as interstitial edema, polymorphonuclear cell infiltration, and acinar cell necrosis in the pancreas. KF24345 (10 mg/kg p.o.) ameliorated all these changes observed in mice with acute pancreatitis, and the suppressing effect of KF24345 on the elevation in serum amylase activity was abolished by the treatment with 8-(p-sulfophenyl)theophylline, an adenosine receptor antagonist. In addition, 2-(aminocarbonyl)- -(4-amino-2,6-dichlorophenyl)-4-[5,5-bis-(4-fluorophenyl)pentyl]-1-piperazineacetamide (R75231) and dipyridamole, other adenosine uptake inhibitors, also decreased the elevated serum amylase activity.
  
  
  CONCLUSIONS
  These are the first demonstrations that the adenosine uptake inhibitors ameliorate cerulein-induced acute pancreatitis in mice, and these data suggest that adenosine uptake inhibition could ameliorate the severity of acute pancreatitis in vivo.
authors.affiliation: Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan. tohru.noji@kyowa.co.jp
authors.forename: Tohru
authors.initials: T
authors.lastname: Noji
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Nan-ya
authors.forename: Chikako
authors.initials: C
authors.lastname: Katagiri
authors.forename: Mirai
authors.initials: M
authors.lastname: Mizutani
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Karasawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kusaka
mesh_terms: D000208:Acute Disease; D000241:Adenosine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000681:Amylases / Q000097:blood; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002108:Ceruletide; D004176:Dipyridamole / Q000494:pharmacology; D005260:Female; D008049:Lipase / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008956:Models, Chemical; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology; D011744:Pyrimidinones / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D011799:Quinazolines / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C444645:3-(1-(6,7-diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl)-1,6-dimethyl-2,4-(1H,3H)-quinazolinedione; D010879:Piperazines; D011744:Pyrimidinones; D011799:Quinazolines; C072040:draflazine; D004176:Dipyridamole; C031433:8-(4-sulfophenyl)theophylline; D002108:Ceruletide; D013806:Theophylline; D008049:Lipase; D000681:Amylases; D000241:Adenosine