Bombesin-induced cytosolic Ca2+spiking in pancreatic acinar cells depends on cyclic ADP-ribose and ryanodine receptors

Cell Calcium ◽  
2001 ◽  
Vol 29 (3) ◽  
pp. 211-216 ◽  
Author(s):  
D. Burdakov ◽  
J.M. Cancela ◽  
O.H. Petersen
Keyword(s):  
Ryanodine Receptors ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Cyclic Adp Ribose

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 Cluster of Differentiation 38 (CD38) Mediates Bile Acid-induced Acinar Cell Injury and Pancreatitis through Cyclic ADP-ribose and Intracellular Calcium Release

2013 ◽  
Vol 288 (38) ◽  
pp. 27128-27137 ◽  
Author(s):  
Abrahim I. Orabi ◽  
Kamaldeen A. Muili ◽  
Tanveer A. Javed ◽  
Shunqian Jin ◽  
Thottala Jayaraman ◽  
...  
Keyword(s):  
Bile Acid ◽  
Ryanodine Receptor ◽  
Acinar Cell ◽  
Calcium Release ◽  
Cell Injury ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Iodide Uptake ◽  
Cyclic Adp Ribose ◽  
Intracellular Ca

Aberrant Ca2+ signals within pancreatic acinar cells are an early and critical feature in acute pancreatitis, yet it is unclear how these signals are generated. An important mediator of the aberrant Ca2+ signals due to bile acid exposure is the intracellular Ca2+ channel ryanodine receptor. One putative activator of the ryanodine receptor is the nucleotide second messenger cyclic ADP-ribose (cADPR), which is generated by an ectoenzyme ADP-ribosyl cyclase, CD38. In this study, we examined the role of CD38 and cADPR in acinar cell Ca2+ signals and acinar injury due to bile acids using pharmacologic inhibitors of CD38 and cADPR as well as mice deficient in Cd38 (Cd38−/−). Cytosolic Ca2+ signals were imaged using live time-lapse confocal microscopy in freshly isolated mouse acinar cells during perifusion with the bile acid taurolithocholic acid 3-sulfate (TLCS; 500 μm). To focus on intracellular Ca2+ release and to specifically exclude Ca2+ influx, cells were perifused in Ca2+-free medium. Cell injury was assessed by lactate dehydrogenase leakage and propidium iodide uptake. Pretreatment with either nicotinamide (20 mm) or the cADPR antagonist 8-Br-cADPR (30 μm) abrogated TLCS-induced Ca2+ signals and cell injury. TLCS-induced Ca2+ release and cell injury were reduced by 30 and 95%, respectively, in Cd38-deficient acinar cells compared with wild-type cells (p < 0.05). Cd38-deficient mice were protected against a model of bile acid infusion pancreatitis. In summary, these data indicate that CD38-cADPR mediates bile acid-induced pancreatitis and acinar cell injury through aberrant intracellular Ca2+ signaling.

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.

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 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
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