| Biliary acute pancreatitis in mice is mediated by the G-protein-coupled cell surface bile acid receptor Gpbar1. | |
| | |
MedLine Citation:
|
PMID: 19900448 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND & AIMS: The mechanisms by which reflux of bile acids into the pancreas induces pancreatitis are unknown. We reasoned that key events responsible for this phenomenon might be mediated by Gpbar1, a recently identified and widely expressed G-protein-coupled, cell surface bile acid receptor. METHODS: Acute pancreatitis was induced in wild-type and Gpbar1(-/-) mice by either retrograde ductal infusion of taurolithocholic acid-3-sulfate (TLCS) or supramaximal secretagogue stimulation with caerulein. In vitro experiments were performed in which acini obtained from wild-type and Gpbar1(-/-) mice were exposed to either submicellar concentrations of TLCS (200-500 microM) or a supramaximally stimulating concentration of caerulein (10 nM). RESULTS: Gpbar1 is expressed at the apical pole of acinar cells and its genetic deletion is associated with reduced hyperamylasemia, edema, inflammation, and acinar cell injury in TLCS-induced, but not caerulein-induced, pancreatitis. In vitro, genetic deletion of Gpbar1 is associated with markedly reduced generation of pathological calcium transients, intracellular activation of digestive zymogens, and cell injury when these responses are induced by exposure to TLCS, but not when they are induced by exposure to caerulein. CONCLUSIONS: Gpbar1 may play a critical role in the evolution of bile-acid-induced pancreatitis by coupling exposure to bile acids with generation of pathological intracellular calcium transients, intra-acinar cell zymogen activation, and acinar cell injury. Acute biliary pancreatitis may be a "receptor-mediated" disease and interventions that interfere with Gpbar1 function might prove beneficial in the treatment and/or prevention of biliary acute pancreatitis. |
| | |
Authors:
|
George Perides; Johanna M Laukkarinen; Galya Vassileva; Michael L Steer |
Related Documents
:
|
18838258 - Glandular stem cells are a promising source for much more than beta-cell replacement. 6997368 - Glicentin and gastric inhibitory polypeptide immunoreactivity in endocrine cells of the... 6260058 - Islet cell adenomatosis: a report of two cases and review of the literature. 6363818 - Immunoreactivity of n-terminal fragment of gastrin-releasing peptide as histochemical m... 14691178 - Thioltranferase mediated ascorbate recycling in human lens epithelial cells. 12566428 - The role of the lissencephaly protein pac1 during nuclear migration in budding yeast. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-11-10 |
Journal Detail:
|
Title: Gastroenterology Volume: 138 ISSN: 1528-0012 ISO Abbreviation: Gastroenterology Publication Date: 2010 Feb |
Date Detail:
|
Created Date: 2010-02-09 Completed Date: 2010-04-01 Revised Date: 2011-09-26 |
Medline Journal Info:
|
Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States |
Other Details:
|
Languages: eng Pagination: 715-25 Citation Subset: AIM; IM |
Affiliation:
|
Department of Surgery, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts 02111, USA. gperides@tuftsmedicalcenter.org |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acute Disease Amylases / metabolism Animals Bile Acids and Salts / metabolism* Caerulein / adverse effects Calcium Signaling / physiology Disease Models, Animal Enzyme Precursors / metabolism GTP-Binding Proteins / metabolism* Mice Mice, Inbred C57BL Mice, Knockout Pancreas / metabolism, pathology Pancreatitis / chemically induced, metabolism* Receptors, G-Protein-Coupled / genetics, metabolism* Severity of Illness Index Taurolithocholic Acid / adverse effects, analogs & derivatives |
| Grant Support | |
ID/Acronym/Agency:
|
P30-NS047423/NS/NINDS NIH HHS; R0-1 31396//PHS HHS; R01 DK031396-27/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Bile Acids and Salts; 0/Enzyme Precursors; 0/Gpbar1 protein, mouse; 0/Receptors, G-Protein-Coupled; 15324-65-9/taurolithocholic acid 3-sulfate; 17650-98-5/Caerulein; 516-90-5/Taurolithocholic Acid; EC 3.2.1.-/Amylases; EC 3.6.1.-/GTP-Binding Proteins |
| Comments/Corrections | |
Comment In:
|
Gastroenterology. 2010 Feb;138(2):429-33
[PMID:
20034603
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: NFAT-induced histone acetylation relay switch promotes c-Myc-dependent growth in pancreatic cancer c...
Next Document: Risk and epidemiological time trends of gastric cancer in Lynch syndrome carriers in the Netherlands...