Bile acid effects are mediated by ATP release and purinergic signalling in exocrine pancreatic cells

Cell Communication and Signaling

Research Article

Nynne M. Christensen¹  Justyna M. Kowal¹  Ivana Novak¹  Kristian A. Haanes² 

[1] Department of Biology, Section for Cell Biology and Physiology, August Krogh Building, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen, Denmark;Department of Biology, Section for Cell Biology and Physiology, August Krogh Building, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen, Denmark;Present address: Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital, Glostrup, Denmark;

关键词: ATP release;    P2 receptors;    Bile acids;    CDCA;    TGR5;    FXR;    Ca;    Pancreas;    ATP sensor;    AT1.03;    FLIM-FRET;   

DOI  :  10.1186/s12964-015-0107-9

 received in 2015-01-28, accepted in 2015-05-26,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundIn many cells, bile acids (BAs) have a multitude of effects, some of which may be mediated by specific receptors such the TGR5 or FXR receptors. In pancreas systemic BAs, as well as intra-ductal BAs from bile reflux, can affect pancreatic secretion. Extracellular ATP and purinergic signalling are other important regulators of similar secretory mechanisms in pancreas. The aim of our study was to elucidate whether there is interplay between ATP and BA signalling.ResultsHere we show that CDCA (chenodeoxycholic acid) caused fast and concentration-dependent ATP release from acini (AR42J) and duct cells (Capan-1). Taurine and glycine conjugated forms of CDCA had smaller effects on ATP release in Capan-1 cells. In duct monolayers, CDCA stimulated ATP release mainly from the luminal membrane; the releasing mechanisms involved both vesicular and non-vesicular secretion pathways. Duct cells were not depleted of intracellular ATP with CDCA, but acinar cells lost some ATP, as detected by several methods including ATP sensor AT1.03YEMK. In duct cells, CDCA caused reversible increase in the intracellular Ca2+ concentration [Ca2 +]i, which could be significantly inhibited by antagonists of purinergic receptors. The TGR5 receptor, expressed on the luminal side of pancreatic ducts, was not involved in ATP release and Ca2+ signals, but could stimulate Na+/Ca2+ exchange in some conditions.ConclusionsCDCA evokes significant ATP release that can stimulate purinergic receptors, which in turn increase [Ca2+]i. The TGR5 receptor is not involved in these processes but can play a protective role at high intracellular Ca2+ conditions. We propose that purinergic signalling could be taken into consideration in other cells/organs, and thereby potentially explain some of the multifaceted effects of BAs.

【 授权许可】

Unknown   
© Kowal et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.