Basic—Liver, Pancreas, and Biliary TractBiliary Acute Pancreatitis in Mice is Mediated by the G-Protein−Coupled Cell Surface Bile Acid Receptor Gpbar1
Section snippets
Materials and Methods
All experiments conformed to protocols approved by the Tufts Medical Center Animal Care and Use Committee. Most reagents, including tetrodotoxin, caerulein TLCS, and Na-taurocholate were purchased from Sigma (St Louis, MO). Fura 2/AM and 1,2-bis(2-aminophenoxy)ethane-N,N,N,N'-tetraacetic acid (BAPTA), were from Molecular Probes (Eugene, OR). Substrates for measuring trypsin and chymotrypsin activity were from Peptides International (Louisville, KY) and substrates for lactate dehydrogenase (LDH)
Bile Acid Receptor Gpbar1 is Expressed in the Pancreas
Gpbar1 expression in the pancreas of wild-type mice can be demonstrated by reverse transcriptase polymerase chain reaction (Figure 1) and it is lost following genetic deletion of Gpbar1. Immunofluorescence microscopy with a Leica TCS SP2 confocal microscope (Figure 1) indicates that most of the anti-Gpbar1 staining is localized to the region very near, but not identical, to the location of f-actin at the acinar cell apical pole. Positive Gpbar1 stain was also seen in gallbladder of wild-type
Discussion
Recent reports have indicated that, in addition to playing an essential role in dietary lipid absorption and cholesterol metabolism, bile acids can also act as signaling molecules. In this capacity, after being taken up by target cells, bile acids can regulate the expression of bile acid transporters by activating nuclear hormone receptors such as the farnesoid X receptor and the pregnane X receptor25, 26, 27 and they can directly activate mitogen-activated protein kinase pathways.28, 29
Acknowledgments
The authors are grateful to Dr Lovy–Wheeler for help with confocal microscopy.
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by National Institutes of Health grant RO-1 31396 from National Institute of Diabetes, Digestive and Kidney Diseases (M.L.S.), P30-NS047423 and by a fellowship from Sigrid Jusélius Foundation, Finland (J.M.L.).