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Bile-pancreatic duct ligation in rats excludes bile-pancreatic juice from gut and induces acute pancreatitis. CCK-A and c:holinergic receptor-mediated exocr/ne pancreatic hyperstimulation secondat 7 to bile-pancreatic juice exclusion ~ implicated in disease pathogenesis. Stimulation of these G protein coupled receptors can activate the Akt-NFkB pathway Nuclear Transcrip~ lion Factor kappa B (NFkB) is a downstream messenger of acinar cell signal transduction via the Akt pathway and is capable o/inr Nag adnar cell cytokina production. We hypothesize that the Akt-NFkB pathway is activated in figation-induced acute pancreatitis. METHODS: We studied rats w~th 1, 3, or 24 hra ot duct ligation or sham-operation (ducts dLssected but not ligated)(n= 5 rats/group). RESULTS: Compared to sham-controls, duct ligation induced acute pancreatitis as evidenced by hyperamylasemia and pancreatic morphologic changes. Electro-mobility shift assay showed a irma-dependent incraase in NFkB in pancreatic nuclear extracts after duct ligation (transcnption factor E-box was used as control; competing cold NFkB prone excluded non-specihc binding), immunobIot analysis of pancreatic homogehates showed mcreases in phospho-Akt and phospho-lkB that were also time-dependent and parallel with NFkB activation (actin immunobiots confirmed equal loadtirg of lanes) (lkB phosphorylation permits translocatinn of NFkB from the cytosol to the nucleus). CONCLUSIONS: 'Paere is a time-dependem and parallel increase in nuclear translocation of NFkB and acuvation of Akt and IkB after duct ligationdnduced acute pancreatitis in rats. These findings are consistent wuh the h)~otbesis that the Akt-NFkB pathway is activated in duct ligation induced acute pancreatitis. In this expemnentaI corollary of gallstone-reduced acute pancreatitts, bile-pancreatic juice exclusion-induced stimulation of acinar cell G protein coupled receptors could exacerbate acute pancreatitis by increased acinar cell production of pro-inflammatory cytokines via lbe Akt-NFkB pathway (Support: Carver Collaborative Pilot Grant; N1H #lK08DK062805)