Abstract | INTRODUCTION: AIMS AND METHODOLOGY: RESULTS: In rats pretreated with PD98059 (10 mg/kg per i.v. injection) or U0126 (5 mg/kg per i.v. injection) 30 minutes before and then together with hourly cerulein injections for 3 hours, pancreatitis was significantly attenuated on the basis of pancreatic wet weight and histology. Serum amylase concentration was significantly reduced when PD98059 was administered intraperitoneally (10 mg/kg per intraperitoneal injection). PD98059 also ameliorated pancreatitis over a 6-hour cerulein time course. The phosphorylation of pancreatic ERK1/2 was attenuated in PD98059- and U0126-treated animals at both 30 minutes and 3 hours after cerulein injection. Rats rendered neutropenic with vinblastine and pretreated with U0126 still showed attenuated manifestations of cerulein-induced acute pancreatitis, a finding suggesting that pancreatic ERK1/2 is mostly responsible for the effect, rather than infiltrating neutrophils. CONCLUSIONS: Inhibition of pancreatic ERK1/2 in vivo affords significant protection against inflammatory sequelae following cerulein-induced acute pancreatitis.
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Authors | Antoinette P Clemons, Deborah M Holstein, Aurelio Galli, Christine Saunders |
Journal | Pancreas
(Pancreas)
Vol. 25
Issue 3
Pg. 251-9
(Oct 2002)
ISSN: 1536-4828 [Electronic] United States |
PMID | 12370536
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Butadienes
- Enzyme Inhibitors
- Flavonoids
- Nitriles
- U 0126
- Ceruletide
- Protein-Tyrosine Kinases
- Protein Serine-Threonine Kinases
- Mitogen-Activated Protein Kinases
- MAP Kinase Kinase 1
- MAP Kinase Kinase 2
- Mitogen-Activated Protein Kinase Kinases
- 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Topics |
- Acute Disease
- Animals
- Butadienes
(pharmacology)
- Ceruletide
- Enzyme Inhibitors
(pharmacology)
- Flavonoids
(pharmacology)
- MAP Kinase Kinase 1
- MAP Kinase Kinase 2
- Male
- Mitogen-Activated Protein Kinase Kinases
(antagonists & inhibitors)
- Mitogen-Activated Protein Kinases
(antagonists & inhibitors)
- Nitriles
(pharmacology)
- Pancreatitis
(chemically induced, drug therapy, enzymology, pathology)
- Protein Serine-Threonine Kinases
(antagonists & inhibitors)
- Protein-Tyrosine Kinases
(antagonists & inhibitors)
- Rats
- Rats, Sprague-Dawley
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