Bile Acids and Pancreatic Disease



Fig. 12.1
A schema of bile acid signaling in pancreatic acinar cells. Extracellular bile acid enters pancreatic acinar cells through Na+-dependent transporter Ntcp at the luminal membrane and Na+-independent transporter Oatp at the basolateral membrane. Cytosolic bile acid induces intracellular Ca2+ overload to activate iP3R, RyRs, and Orai channel and to inhibit SERCA pump. Intracellular Ca2+ overload induces MPTP opening and subsequent acinar cell necrosis by ATP depletion. On the other hand, ROS and intracellular Ca2+ overload can induce acinar cell apoptosis by cytochrome c/caspase pathway, as well. The intercellular signaling of bile acid receptor Gpbar1 in pancreatic acinar cells is still largely unknown. Gpbar1 G protein-coupled bile acid receptor, Ntcp Na+-taurocholate cotransporting polypeptide, Oatp organic anion-transporting polypeptide, IP 3 R inositol trisphosphate receptor, RyRs ryanodine receptors, SERCA sarco/endoplasmic reticulum Ca2+ ATPase, STIM stromal interaction molecule, ROS Reactive oxygen species, MPTP mitochondrial permeability transition pore, ATP adenosine triphosphate



Thus, some of the molecular mechanisms by which bile acids induce acute pancreatitis have been elucidated so far. Importantly, there have been several experimental therapeutic attempts to identify molecular targets for preventing the processes of bile acid-induced acute pancreatitis.



References



1.

Lankish PG, Apte M, Banks PA. Acute pancreatitis. Lancet. 2015;386(9988):85–96. doi:10.​1016/​S0140-6736(14)60649-8.CrossRef


2.

Hamada S, Masamune A, Kikuta K, Hirota M, Tsuji I, Shimosegawa T. Research committee of intractable disease of the pancreas. Nationwide epidemiological survey of acute pancreatitis in Japan. Pancreas. 2014;43(8):1244–8. doi:10.​1097/​MPA.​0000000000000200​.CrossRefPubMed


3.

Lerch MM, Aghdassi AA. The role of bile acids in gallstone-induced pancreatitis. Gastroenterology. 2010;138(2):429–33. doi:10.​1016/​j.​bpg.​2009.​02.​013.CrossRefPubMed


4.

Chan YC, Leung PS. Acute pancreatitis: animal models and recent advances in basic research. Pancreas. 2007;34(1):1–14.CrossRefPubMed


5.

Su KH, Cuthbertson C, Christophi C. Review of experimental animal models of acute pancreatitis. HPB. 2006;8(4):264–86. doi:10.​1080/​1365182050046735​8.CrossRefPubMed


6.

Wan MH, Huang W, Latawiec D, Jiang K, Booth DM, Elliott V, Mukherjee R, Xia Q. HPB. 2012;14(2):73–81. doi:10.​1111/​j.​1477-2574.​2011.​00408.​x.CrossRefPubMedPubMedCentral


7.

Kruger B, Albrecht E, Lerch MM. The role of intracellular calcium signaling in premature protease activation and the onset of pancreatitis. Am J Pathol. 2000;157(1):43–50.CrossRefPubMedPubMedCentral

Aug 29, 2017 | Posted by in GASTROENTEROLOGY | Comments Off on Bile Acids and Pancreatic Disease

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