title: Specific type IV phosphodiesterase inhibitor ameliorates cerulein-induced pancreatitis in rats.
abstract: OBJECTIVE
  Type IV phosphodiesterase is a key enzyme to metabolize intracellular adenosine 3',5'-cyclic monophosphate (cAMP) expressed in inflammatory cells. The specific type IV phosphodiesterase inhibitor that increases intracellular cAMP is known to be potent suppressor of proinflammatory cytokines. However, the effect of phosphodiesterase inhibitors on the development of pancreatitis has not been well understood. In the present study, we examined the effect of a specific type IV phosphodiesterase inhibitor on experimentally induced pancreatitis.
  
  
  METHODS
  Severity of cerulein-induced pancreatitis and pancreatic proinflammatory cytokine levels were studied with or without pretreatment with a specific type IV phosphodiesterase inhibitor (rolipram) in Sprague-Dawley rats.
  
  
  RESULTS
  Administration of rolipram clearly ameliorated severity of pancreatitis evaluated by edema, serum amylase (P<0.05), and lipase levels (P<0.05) in rats. Also, the level of pancreatic proinflammatory cytokine (interleukin-1beta (IL-1beta)) was significantly reduced when rats were treated with rolipram prior cerulein injection (P<0.05).
  
  
  CONCLUSIONS
  Our results demonstrated that intracellular cAMP and pancreatic proinflammatory cytokine level, which are regulated by type IV phosphodiesterase, might play an important role in the pathogenesis of acute pancreatitis.
authors.affiliation: Department of Internal Medicine-1, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sato
authors.forename: Michiro
authors.initials: M
authors.lastname: Otaka
authors.forename: Masaru
authors.initials: M
authors.lastname: Odashima
authors.forename: Sayuri
authors.initials: S
authors.lastname: Kato
authors.forename: Mario
authors.initials: M
authors.lastname: Jin
authors.forename: Noriaki
authors.initials: N
authors.lastname: Konishi
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Matsuhashi
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002108:Ceruletide; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D002108:Ceruletide; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram