title: Rolipram and SP600125 suppress the early increase in PTP1B expression during cerulein-induced pancreatitis in rats.
abstract: OBJECTIVE
  To analyze the expression modulation of pancreatic protein tyrosine phosphatase (PTP)1B during the development of cerulein (Cer)-induced acute pancreatitis (AP) and the effect of inhibition of type 4 phosphodiesterase and c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 on its expression levels.
  
  
  METHODS
  Acute pancreatitis was induced in rats by subcutaneous injections of 20 microg Cer per kilogram body weight at hourly intervals, and the animals were killed at 2, 4, or 9 hours after the first injection. Neutropenia was induced with vinblastine sulfate. Phosphodiesterase and the mitogen-activated protein kinases were inhibited with rolipram and SP600125, respectively, before the induction of AP.
  
  
  RESULTS
  Protein tyrosine phosphatase 1B increases its expression at the levels of both protein and messenger RNA during the early phase of Cer-induced AP. The increase in protein expression persisted along the development of the disease, and neutrophil infiltration seemed to play a central role. Rolipram and SP600125 pretreatments mostly suppressed the increase in the expression of PTP1B during the early phase of AP.
  
  
  CONCLUSIONS
  Cerulein-induced AP is associated with an increase in the expression of PTP1B in its early phase. An increase in cyclic adenosine monophosphate levels in inflammatory cells and the inhibition of c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 are able to suppress the increase in PTP1B protein level.
authors.affiliation: Department of Biochemistry, University of Salamanca, Salamanca, Spain.
authors.forename: Nancy
authors.initials: N
authors.lastname: Sarmiento
authors.forename: Carmen
authors.initials: C
authors.lastname: Sánchez-Bernal
authors.forename: Nieves
authors.initials: N
authors.lastname: Pérez
authors.forename: José L
authors.initials: JL
authors.lastname: Sardina
authors.forename: Arturo
authors.initials: A
authors.lastname: Mangas
authors.forename: José J
authors.initials: JJ
authors.lastname: Calvo
authors.forename: Jesús
authors.initials: J
authors.lastname: Sánchez-Yagüe
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000627:therapeutic use*; D002108:Ceruletide / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D048031:JNK Mitogen-Activated Protein Kinases / Q000032:analysis / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000032:analysis / Q000378:metabolism; D009503:Neutropenia / Q000139:chemically induced; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000627:therapeutic use*; D014747:Vinblastine / Q000009:adverse effects
chemical_list: D000873:Anthracenes; D010726:Phosphodiesterase Inhibitors; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D014747:Vinblastine; D002108:Ceruletide; D000242:Cyclic AMP; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram