Cholinergic receptor induction and JNK activation in acute pancreatitis.
BACKGROUND
Cholecystokinin-A (CCK-A) and cholinergic receptor pathways, capable of activating stress kinases p38 mitogen-activated protein kinase (p38(MAPK)) and cJUN N-terminal kinase (JNK), are implicated in the pathogenesis of ligation-induced acute pancreatitis in rats. As ligation-induced acute pancreatitis in rats is associated with CCK-A receptor induction and p38(MAPK) activation, and as receptor induction could amplify acinar hyperstimulation and exacerbate cell stress, we tested the hypothesis that the cholinergic M3 receptor is induced and JNK is activated in this model.


METHODS
Cholinergic M3 receptor expression and JNK activation was compared in rats 1, 3, or 24 hours after sham operation or duct ligation.


RESULTS
Immunoblot analysis of pancreatic homogenates showed a time-dependent increase in cholinergic M3 receptor protein, total JNK, and phospho-JNK after duct ligation.


CONCLUSIONS
There is a rapid and progressive cholinergic M3 receptor induction and JNK activation in ligation-induced acute pancreatitis in rats. These findings may have significance in the mechanism of disease pathogenesis.
Department of Surgery, Veterans Affairs Medical Center, University of Iowa Roy J. and Lucille A. Carver College of Medicine, 200 Hawkins Drive, 4625 JCP, Iowa City, IA 52242, USA. Isaac-samuel@uiowa.edu
Isaac
I
Samuel
Smita
S
Zaheer
Rory A
RA
Fisher
Asgar
A
Zaheer
D000208:Acute Disease; D000818:Animals; D004789:Enzyme Activation; D015151:Immunoblotting; D048031:JNK Mitogen-Activated Protein Kinases; D008026:Ligation; D048670:MAP Kinase Kinase 4; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis*; D010183:Pancreatic Ducts / Q000601:surgery; D010195:Pancreatitis / Q000209:etiology / Q000378:metabolism*; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013997:Time Factors
D011950:Receptors, Cholinergic; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases