scholarly journals Bile acids activate ryanodine receptors in pancreatic acinar cells via a direct allosteric mechanism

Cell Calcium ◽  
2015 ◽  
Vol 58 (2) ◽  
pp. 160-170 ◽  
Author(s):  
Nikolett Geyer ◽  
Gyula Diszházi ◽  
László Csernoch ◽  
István Jóna ◽  
János Almássy
Keyword(s):  
Bile Acids ◽  
Ryanodine Receptors ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Allosteric Mechanism

scholarly journals Localized Ca2+ uncaging reveals polarized distribution of Ca2+-sensitive Ca2+ release sites

2002 ◽  
Vol 158 (2) ◽  
pp. 283-292 ◽  
Author(s):  
Michael C. Ashby ◽  
Madeleine Craske ◽  
Myoung Kyu Park ◽  
Oleg V. Gerasimenko ◽  
Robert D. Burgoyne ◽  
...  
Keyword(s):  
Ryanodine Receptors ◽  
Acinar Cells ◽  
Cell Types ◽  
Pancreatic Acinar Cells ◽  
Apical Region ◽  
Basal Region ◽  
Activation Pattern ◽  
Inositol Trisphosphate Receptors ◽  
Agonist Stimulation ◽  
Major Process

Ca2+-induced Ca2+ release (CICR) plays an important role in the generation of cytosolic Ca2+ signals in many cell types. However, it is inherently difficult to distinguish experimentally between the contributions of messenger-induced Ca2+ release and CICR. We have directly tested the CICR sensitivity of different regions of intact pancreatic acinar cells using local uncaging of caged Ca2+. In the apical region, local uncaging of Ca2+ was able to trigger a CICR wave, which propagated toward the base. CICR could not be triggered in the basal region, despite the known presence of ryanodine receptors. The triggering of CICR from the apical region was inhibited by a pharmacological block of ryanodine or inositol trisphosphate receptors, indicating that global signals require coordinated Ca2+ release. Subthreshold agonist stimulation increased the probability of triggering CICR by apical uncaging, and uncaging-induced CICR could activate long-lasting Ca2+ oscillations. However, with subthreshold stimulation, CICR could still not be initiated in the basal region. CICR is the major process responsible for global Ca2+ transients, and intracellular variations in sensitivity to CICR predetermine the activation pattern of Ca2+ waves.

scholarly journals Bile Acids Induce a Cationic Current, Depolarizing Pancreatic Acinar Cells and Increasing the Intracellular Na+Concentration

2004 ◽  
Vol 280 (3) ◽  
pp. 1764-1770 ◽  
Author(s):  
Svetlana G. Voronina ◽  
Olexyi V. Gryshchenko ◽  
Oleg V. Gerasimenko ◽  
Anne K. Green ◽  
Ole H. Petersen ◽  
...  
Keyword(s):  
Bile Acids ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Cationic Current

scholarly journals Spatial characterisation of ryanodine-induced calcium release in mouse pancreatic acinar cells

2003 ◽  
Vol 369 (3) ◽  
pp. 441-445 ◽  
Author(s):  
Michael C. ASHBY ◽  
Ole H. PETERSEN ◽  
Alexei V. TEPIKIN
Keyword(s):  
Experimental Data ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Apical Region ◽  
Low Doses ◽  
Polarized Cells ◽  
Inositol 1,4,5 Trisphosphate ◽  
Increased Sensitivity

In pancreatic acinar cells, agonists evoke intracellular Ca2+ transients which are initiated in the apical region of these polarized cells. There are contradictory experimental data concerning Ca2+ release from ryanodine receptors (RyRs) in the apical region. In the present study, we have used low doses of ryanodine to open RyRs leading to the release of Ca2+ from intracellular stores. Ryanodine causes Ca2+ release that is initiated in the apical region of the cell but is dependent upon functional inositol 1,4,5-trisphosphate receptors (IP3Rs). These results suggests that co-ordinated release from co-localized RyRs and IP3Rs underlies the increased sensitivity of the apical region to initiation of intracellular Ca2+ transients.

scholarly journals Bile acids induce calcium signals in mouse pancreatic acinar cells: implications for bile‐induced pancreatic pathology

2002 ◽  
Vol 540 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Svetlana Voronina ◽  
Rebecca Longbottom ◽  
Robert Sutton ◽  
Ole H. Petersen ◽  
Alexei Tepikin
Keyword(s):  
Bile Acids ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Calcium Signals ◽  
Pancreatic Pathology

1023 Alcohol Predisposes to Pathologic Calcium Signals in Pancreatic Acinar Cells by Hyper-Phosphorylating Ryanodine Receptors

2010 ◽  
Vol 138 (5) ◽  
pp. S-149
Author(s):  
Abrahim I. Orabi ◽  
Ahsan U. Shah ◽  
Zahir M. Mannan ◽  
Mahwish U. Ahmad ◽  
Xingtie Nie ◽  
...  
Keyword(s):  
Ryanodine Receptors ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Calcium Signals

scholarly journals The role of intracellular Ca2+ signaling in the exocrine pancreatic damage during acute pancreatitis

2020 ◽  
Author(s):  
Júlia Fanczal
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Bile Acid ◽  
Bile Acids ◽  
Digestive Enzyme ◽  
Acinar Cells ◽  
Mitochondrial Damage ◽  
Enzyme Activation ◽  
Pancreatic Acinar Cells ◽  
Biliary Pancreatitis

Acute biliary pancreatitis poses a significant clinical challenge as currently no specific pharmaceutical treatment exists. Disturbed intracellular Ca2+ signalling caused by bile acids is a hallmark of the disease, which induces increased reactive oxygen species (ROS) production, mitochondrial damage, intra-acinar digestive enzyme activation and cell death. Because of this mechanism of action, prevention of toxic cellular Ca2+ overload is a promising therapeutic target. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel that has recently emerged as an important contributor to oxidative-stress-induced cellular Ca2+ overload across different diseases. However, the expression and possible functions of TRPM2 in the exocrine pancreas remain unknown. Here we found that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar, which can be activated by increased oxidative stress induced by H2O2 treatment. TRPM2 activity was found to contribute to bile acid-induced extracellular Ca2+ influx in acinar cells. The generation of intracellular ROS in response to bile acids was remarkably higher in pancreatic acinar cells. This activity promoted acinar cell necrosis in vitro independently from mitochondrial damage or mitochondrial fragmentation. In addition, bile-acid-induced experimental pancreatitis was less severe in TRPM2 knockout mice, whereas the lack of TRPM2 had no protective effect in cerulein-induced acute pancreatitis. Our results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis.

Phosphatidylinositol 3-kinase facilitates bile acid-induced Ca2+ responses in pancreatic acinar cells

2007 ◽  
Vol 292 (3) ◽  
pp. G875-G886 ◽  
Author(s):  
L. Fischer ◽  
A. S. Gukovskaya ◽  
J. M. Penninger ◽  
O. A. Mareninova ◽  
H. Friess ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Inhibitors ◽  
Trypsinogen Activation ◽  
Plasmic Reticulum ◽  
Intracellular Ca ◽  
Phosphatidylinositol 3

Bile acids are known to induce Ca2+ signals in pancreatic acinar cells. We have recently shown that phosphatidylinositol 3-kinase (PI3K) regulates changes in free cytosolic Ca2+ concentration ([Ca2+]i) elicited by CCK by inhibiting sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA). The present study sought to determine whether PI3K regulates bile acid-induced [Ca2+]i responses. In pancreatic acinar cells, pharmacological inhibition of PI3K with LY-294002 or wortmannin inhibited [Ca2+]i responses to taurolithocholic acid 3-sulfate (TLC-S) and taurochenodeoxycholate (TCDC). Furthermore, genetic deletion of the PI3K γ-isoform also decreased [Ca2+]i responses to bile acids. Depletion of CCK-sensitive intracellular Ca2+ pools or application of caffeine inhibited bile acid-induced [Ca2+]i signals, indicating that bile acids release Ca2+ from agonist-sensitive endoplasmic reticulum (ER) stores via an inositol ( 1 , 4 , 5 )-trisphosphate-dependent mechanism. PI3K inhibitors increased the amount of Ca2+ in intracellular stores during the exposure of acinar cells to bile acids, suggesting that PI3K negatively regulates SERCA-dependent Ca2+ reloading into the ER. Bile acids inhibited Ca2+ reloading into ER in permeabilized acinar cells. This effect was augmented by phosphatidylinositol ( 3 , 4 , 5 )-trisphosphate (PIP3), suggesting that both bile acids and PI3K act synergistically to inhibit SERCA. Furthermore, inhibition of PI3K by LY-294002 completely inhibited trypsinogen activation caused by the bile acid TLC-S. Our results indicate that PI3K and its product, PIP3, facilitate bile acid-induced [Ca2+]i responses in pancreatic acinar cells through inhibition of SERCA-dependent Ca2+ reloading into the ER and that bile acid-induced trypsinogen activation is mediated by PI3K. The findings have important implications for the mechanism of acute pancreatitis since [Ca2+]i increases and trypsinogen activation mediate key pathological processes in this disorder.

scholarly journals Effects of Secretagogues and Bile Acids on Mitochondrial Membrane Potential of Pancreatic Acinar Cells

2004 ◽  
Vol 279 (26) ◽  
pp. 27327-27338 ◽  
Author(s):  
Svetlana G. Voronina ◽  
Stephanie L. Barrow ◽  
Oleg V. Gerasimenko ◽  
Ole H. Petersen ◽  
Alexei V. Tepikin
Keyword(s):  
Membrane Potential ◽  
Bile Acids ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells
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