CCK-A receptor induction and P38 and NF-kappaB activation in acute pancreatitis.
Bile-pancreatic duct ligation in rats excludes bile-pancreatic juice from the gut and induces acute pancreatitis. Bile-pancreatic juice exclusion from the gut results in increased plasma cholecystokinin (CCK) levels. CCK-A receptor-mediated exocrine pancreatic hyperstimulation is implicated in disease pathogenesis. In the present study, we show for the first time a progressive rise in CCK-A receptor protein expression in ligation-induced acute pancreatitis in rats. As CCK-A receptor induction could amplify CCK-mediated acinar hyperstimulation and exacerbate acinar cell stress with activation of the p38(MAPK) stress kinase pathway, we studied CCK-A receptor protein expression and p38(MAPK) activation in duct ligation-induced acute pancreatitis in rats. Compared to sham-operated controls, acute pancreatitis induced by bile-pancreatic duct ligation associates with a temporal increase in pancreatic CCK-A receptor protein expression, p38(MAPK) expression and activation, and NF-kappaB activation. These findings may have significance in the mechanism of disease pathogenesis in this experimental model.
Department of Surgery, University of Iowa Roy J. and Lucille A. Carver College of Medicine, and the Veterans Affairs Medical Center, Iowa City, Iowa 52242, USA. Isaac-samuel@uiowa.edu
Isaac
I
Samuel
Smita
S
Zaheer
Jeffrey J
JJ
Nelson
Mark A
MA
Yorek
Asgar
A
Zaheer
D000208:Acute Disease; D000818:Animals; D001646:Bile; D004195:Disease Models, Animal; D004789:Enzyme Activation; D015870:Gene Expression; D015151:Immunoblotting; D008026:Ligation; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010183:Pancreatic Ducts / Q000601:surgery; D010195:Pancreatitis / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000096:biosynthesis* / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases
D016328:NF-kappa B; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases