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.
Samuel
Isaac
I
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
Zaheer
Smita
S
Nelson
Jeffrey J
JJ
Yorek
Mark A
MA
Zaheer
Asgar
A
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