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Bile acids induce Ca2+ release from both the endoplasmic reticulum and acidic intracellular calcium stores through activation of inositol trisphosphate receptors and ryanodine receptors

Gerasimenko, Julia Vladimirovna ORCID: https://orcid.org/0000-0002-2262-2543, Flowerdew, S. E., Voronina, S. G., Sukhomlin, T. K., Tepikin, A. V., Petersen, Ole Holger ORCID: https://orcid.org/0000-0002-6998-0380 and Gerasimenko, Oleg Vsevolodovich ORCID: https://orcid.org/0000-0003-2573-8258 2006. Bile acids induce Ca2+ release from both the endoplasmic reticulum and acidic intracellular calcium stores through activation of inositol trisphosphate receptors and ryanodine receptors. Journal of Biological Chemistry 281 (52) , pp. 40154-40163. 10.1074/jbc.M606402200

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Abstract

Gallstones can cause acute pancreatitis, an often fatal disease in which the pancreas digests itself. This is probably because of biliary reflux into the pancreatic duct and subsequent bile acid action on the acinar cells. Because Ca2+ toxicity is important for the cellular damage in pancreatitis, we have studied the mechanisms by which the bile acid taurolithocholic acid 3-sulfate (TLC-S) liberates Ca2+. Using two-photon plasma membrane permeabilization and measurement of [Ca2+] inside intracellular stores at the cell base (dominated by ER) and near the apex (dominated by secretory granules), we have characterized the Ca2+ release pathways. Inhibition of inositol trisphosphate receptors (IP3Rs), by caffeine and 2-APB, reduced Ca2+ release from both the ER and an acidic pool in the granular area. Inhibition of ryanodine receptors (RyRs) by ruthenium red (RR) also reduced TLC-S induced liberation from both stores. Combined inhibition of IP3Rs and RyRs abolished Ca2+ release. RyR activation depends on receptors for nicotinic acid adenine dinucleotide phosphate (NAADP), because inactivation by a high NAADP concentration inhibited release from both stores, whereas a cyclic ADPR-ribose antagonist had no effect. Bile acid-elicited intracellular Ca2+ liberation from both the ER and the apical acidic stores depends on both RyRs and IP3Rs.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Systems Immunity Research Institute (SIURI)
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 0021-9258
Last Modified: 25 Oct 2022 10:10
URI: https://orca.cardiff.ac.uk/id/eprint/61328

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