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

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 Ca(2+) 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 Ca(2+). Using two-photon plasma membrane permeabilization and measurement of [Ca(2+)] inside intracellular stores at the cell base (dominated by ER) and near the apex (dominated by secretory granules), we have characterized the Ca(2+) release pathways. Inhibition of inositol trisphosphate receptors (IP(3)Rs), by caffeine and 2-APB, reduced Ca(2+) 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 IP(3)Rs and RyRs abolished Ca(2+) 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 Ca(2+) liberation from both the ER and the apical acidic stores depends on both RyRs and IP(3)Rs.

• Authors: Julia V Gerasimenko, Sarah E Flowerdew, Svetlana G Voronina, Tatiana K Sukhomlin, Alexei V Tepikin, Ole H Petersen, Oleg V Gerasimenko
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 281 Issue 52 Pg. 40154-63 (Dec 29 2006) ISSN: 0021-9258 [Print] United States
• PMID: 17074764 (Publication Type: Journal Article, Validation Study)

Chemical References

• Inositol 1,4,5-Trisphosphate Receptors
• Ryanodine Receptor Calcium Release Channel
• taurolithocholic acid 3-sulfate
• Caffeine
• Taurolithocholic Acid
• NADP
• NAADP
• Calcium

Topics

• Animals
• Caffeine (pharmacology)
• Calcium (antagonists & inhibitors, metabolism, physiology)
• Endoplasmic Reticulum (chemistry, metabolism)
• Hydrogen-Ion Concentration
• Inositol 1,4,5-Trisphosphate Receptors (antagonists & inhibitors, metabolism, physiology)
• Intracellular Fluid (chemistry, metabolism)
• Male
• Mice
• NADP (analogs & derivatives, antagonists & inhibitors, physiology)
• Pancreas, Exocrine (chemistry, cytology, metabolism)
• Ryanodine Receptor Calcium Release Channel (metabolism, physiology)
• Secretory Vesicles (chemistry, metabolism)
• Signal Transduction (drug effects, physiology)
• Taurolithocholic Acid (analogs & derivatives, antagonists & inhibitors, pharmacology, physiology)