Bile-pancreatic juice exclusion increases cholinergic M3 and CCK-A receptor expression and interleukin-6 production in ligation-induced acute pancreatitis.
BACKGROUND
Using an original model, the Donor Rat Model, we showed that bile-pancreatic juice (BPJ) exclusion from gut exacerbates ligation-induced acute pancreatitis in rats. We also showed that muscarinic cholinergic M3 and CCK-A receptor expression is induced following duct ligation. Increased receptor number potentially could exacerbate cytokine production. We hypothesize that BPJ exclusion is responsible for M3 and CCK-A receptor induction and increased interleukin-6 (IL-6) production.


METHODS
M3 and CCK-A receptor expression and IL-6 production were compared in rat pancreata 1 to 3 hours after duct ligation with or without BPJ replacement.


RESULTS
Our studies showed that BPJ replacement attenuates duct ligation-induced increases in M3 and CCK-A receptor expression and IL-6 production.


CONCLUSIONS
In this model, BPJ exclusion from gut induces M3 and CCK-A receptor expression and increases IL-6 production. In this experimental corollary of gallstone pancreatitis, BPJ exclusion from gut may play a key role in the mechanism of disease pathogenesis.
Samuel
Isaac
I
Department of Surgery, Veterans Affairs Medical Center & University of Iowa Roy J. and Lucille A. Carver College of Medicine, 200 Hawkins Dr., 4625 JCP, Iowa City, IA 52242, USA. Isaac-samuel@uiowa.edu
Zaheer
Asgar
A
Zaheer
Smita
S
Fisher
Rory A
RA
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D015151:Immunoblotting; D015850:Interleukin-6 / Q000096:biosynthesis*; D008026:Ligation / Q000379:methods; D008297:Male; D010189:Pancreatic Juice / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism*; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000032:analysis / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000032:analysis / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000032:analysis / Q000378:metabolism; D012680:Sensitivity and Specificity
D015415:Biomarkers; D015850:Interleukin-6; D043886:Receptor, Cholecystokinin A; D043587:Receptor, Muscarinic M3; D011950:Receptors, Cholinergic