p38 map kinase is expressed in the pancreas and is immediately activated following cerulein hyperstimulation.
BACKGROUND
The pathophysiology of pancreatitis and the pancreatic stress response are not well understood. In the pancreas, mitogen-activated protein kinase (MAPK) and stress-activated protein kinase (SAPK) are reportedly regulated by secretagogue stimulation and hyperstimulation. However, no data exist on the expression and regulation of pancreatic p38 Map kinase.


OBJECTIVE
Pancreatic expression of p38 Map kinase and MAPK, SAPK and p38 regulation during pancreatic stress were investigated.


METHODS
For hyperstimulation and secretory stress, cerulein was given intravenously, while hyperthermia preconditioning stress was induced by whole body hyperthermia (42 degreesC).


RESULTS
In addition to MAPK and SAPK, p38 Map kinase was found to be expressed in the rat pancreas. Cerulein regulated all kinases time- and dose-dependently. MAPK and p38 Map kinase showed basal activity and were further activated at low cerulein doses. SAPK had no basal activity and its activation required maximal secretory to supramaximal amounts of cerulein. Cerulein hyperstimulation, inducing pancreatitis, activated p38 more rapidly than SAPK and more strongly than MAPK. In contrast to cerulein hyperstimulation stress, hyperthermia stress only activated p38 Map kinase.


CONCLUSIONS
p38 Map kinase is expressed in the pancreas and is most rapidly activated following cerulein hyperstimulation. Both SAPK and p38 Map kinase are possibly important regulators during the onset of cerulein pancreatitis.
Wagner
A C
AC
Department of Gastroenterology, University of Bern, Inselspital, Bern, Switzerland.Awagner@dkf4.unibe.ch
Metzler
W
W
Höfken
T
T
Weber
H
H
Göke
B
B
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002108:Ceruletide / Q000494:pharmacology; D004789:Enzyme Activation; D005765:Gastrointestinal Agents / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006979:Hyperthermia, Induced; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010179:Pancreas / Q000201:enzymology*; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases
D005765:Gastrointestinal Agents; D002108:Ceruletide; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases