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Bile Acid and ATP Signaling in Exocrine Pancreatic Cells
Author(s) -
Kowal Justyna,
Haanes Kristian,
Christensen Nynne,
Novak Ivana
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.973.2
Subject(s) - extracellular , purinergic receptor , microbiology and biotechnology , receptor , intracellular , chemistry , acinar cell , ductal cells , calcium in biology , medicine , biology , pancreas , endocrinology , biochemistry
Bile acids (BAs) have a multitude of effects in many cells, some of which are mediated by specific receptors such as the TGR5 receptor (Schaap et al., 2014 Nat. Rev. Gastroenterol. Hepatol. 11 , 55‐67). Pancreatic cells could be exposed to systemic BAs, as well as to intra‐ductal BAs from bile reflux. They could affect secretory function and/or integrity of pancreatic ducts and acini. Extracellular ATP and purinergic signaling have similar regulatory targets as BAs in pancreas (Novak et al., 2013 Front Physiol 4 , 380). The aim of the study was to investigate the interplay between ATP and BA signalling in exocrine pancreas. Using live‐cell detection of extracellular ATP, we show that chenodeoxycholic acid (CDCA) caused fast and concentration‐dependent ATP release from acinar cells, AR42J (614 ± 79 nM; n = 5) and duct cell line, Capan‐1 (848 ± 16 nM; n = 6). In duct monolayers, ATP was released mainly across the luminal membrane via vesicular and non‐vesicular secretory pathways. Duct cells were not depleted of intracellular ATP (ATP i ), but acinar cells lost some ATP i , as detected by several methods including ATP sensor AT1.03 YEMK and Magnesium Green. In duct cells, CDCA caused an increase in the intracellular Ca 2+ [Ca 2+ ] i (177 ± 21 nM, n = 5), which was significantly inhibited by a mix of antagonists of purinergic receptors (90 ± 9 nM, n = 5). The TGR5 receptor is expressed mainly on luminal membrane of duct epithelia and it can stimulate the Na + /Ca 2+ exchanger, protecting cells against high [Ca 2+ ] i . In conclusion, the CDCA effect can be mediated by ATP release and purinergic signalling. We propose that purinergic signalling must be taken into consideration when interpreting the multifaceted effects of BAs. Support: The Danish Council for Independent Research/Natural Sciences (0602‐01527B; 4002‐00162).