scholarly journals Cell Side-specific Sensitivities of Intracellular Ca2+Stores for Inositol 1,4,5-Trisphosphate, Cyclic ADP-ribose, and Nicotinic Acid Adenine Dinucleotide Phosphate in Permeabilized Pancreatic Acinar Cells from Mouse

2002 ◽  
Vol 277 (14) ◽  
pp. 11696-11702 ◽  
Author(s):  
Elmar Krause ◽  
Alexandra Göbel ◽  
Irene Schulz
Keyword(s):  
Nicotinic Acid ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Cyclic Adp Ribose ◽  
Inositol 1,4,5 Trisphosphate

scholarly journals The Ecto-enzyme CD38 Is a Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Synthase That Couples Receptor Activation to Ca2+Mobilization from Lysosomes in Pancreatic Acinar Cells

2010 ◽  
Vol 285 (49) ◽  
pp. 38251-38259 ◽  
Author(s):  
François Cosker ◽  
Nathalie Cheviron ◽  
Michiko Yamasaki ◽  
Alexis Menteyne ◽  
Frances E. Lund ◽  
...  
Keyword(s):  
Nicotinic Acid ◽  
Acinar Cells ◽  
Receptor Activation ◽  
Pancreatic Acinar Cells

Mechanisms of calcium signaling by cyclic ADP-ribose and NAADP

1997 ◽  
Vol 77 (4) ◽  
pp. 1133-1164 ◽  
Author(s):  
H. C. Lee
Keyword(s):  
Nitric Oxide ◽  
Nicotinic Acid ◽  
Live Cells ◽  
Release Mechanism ◽  
Major Mechanism ◽  
Signaling Mechanisms ◽  
Signaling Function ◽  
Cyclic Adp Ribose ◽  
Inositol 1,4,5 Trisphosphate ◽  
External Signals

Cells possess various mechanisms for transducing external signals to intracellular responses. The discovery of inositol 1,4,5-trisphosphate (IP3) as a messenger for mobilizing internal Ca2+ stores has centralized Ca2+ mobilization among signaling mechanisms. Results reviewed in this article establish that, in addition to IP3, the internal Ca2+ stores can be mobilized by at least two other molecules, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), via totally independent mechanisms. Cyclic ADP-ribose is a newly discovered cyclic nucleotide derived from NAD, but, unlike adenosine 3',5'-cyclic monophosphate, its main signaling function is modulation of Ca(2+)-induced Ca2+ release, a major mechanism of Ca2+ mobilization in addition to the IP3 pathway. Evidence shows that cADPR may in fact be responsible for mediating the Ca(2+)-mobilizing activity of the gaseous messenger nitric oxide. Cells responsive to cADPR are widespread and include species from plant to mammal, indicating the generality of cADPR as a signaling molecule. In addition to cADPR, NAADP, a metabolite of NADP, can also mobilize Ca2+ stores. The release mechanism and the stores on which NAADP acts are distinct from cADPR and IP3. Nicotinic acid adenine dinucleotide phosphate may play a role in generating Ca2+ oscillations, since liberation of NAADP in live cells by photolyzing its caged analog produces long lasting Ca2+ oscillations. These two new Ca2+ agonists are intimately related, since the same metabolic enzymes can, under appropriate conditions, synthesize either one, suggesting a unified mechanism may regulate both pathways. Elucidation of these two new Ca2+ mobilization pathways is likely to have an important impact on our understanding of cellular signaling mechanisms.

Effect of intracellular pH on acetylcholine-induced Ca2+ waves in mouse pancreatic acinar cells

1998 ◽  
Vol 275 (3) ◽  
pp. C810-C817 ◽  
Author(s):  
Antonio González ◽  
Fatima Pfeiffer ◽  
Andreas Schmid ◽  
Irene Schulz
Keyword(s):  
Intracellular Ph ◽  
Acinar Cells ◽  
Propagation Rate ◽  
Spreading Speed ◽  
Pancreatic Acinar Cells ◽  
Acidic Ph ◽  
Basolateral Side ◽  
Inositol 1,4,5 Trisphosphate ◽  
The Relationship ◽  
Cytosolic Acidification

We have used fluo 3-loaded mouse pancreatic acinar cells to investigate the relationship between Ca2+ mobilization and intracellular pH (pHi). The Ca2+-mobilizing agonist ACh (500 nM) induced a Ca2+ release in the luminal cell pole followed by spreading of the Ca2+ signal toward the basolateral side with a mean speed of 16.1 ± 0.3 μm/s. In the presence of an acidic pHi, achieved by blockade of the Na+/H+exchanger or by incubation of the cells in a Na+-free buffer, a slower spreading of ACh-evoked Ca2+ waves was observed (7.2 ± 0.6 μm/s and 7.5 ± 0.3 μm/s, respectively). The effects of cytosolic acidification on the propagation rate of ACh-evoked Ca2+ waves were largely reversible and were not dependent on the presence of extracellular Ca2+. A reduction in the spreading speed of Ca2+ waves could also be observed by inhibition of the vacuolar H+-ATPase with bafilomycin A1 (11.1 ± 0.6 μm/s), which did not lead to cytosolic acidification. In contrast, inhibition of the endoplasmic reticulum Ca2+-ATPase by 2,5-di- tert-butylhydroquinone led to faster spreading of the ACh-evoked Ca2+ signals (25.6 ± 1.8 μm/s), which was also reduced by cytosolic acidification or treatment of the cells with bafilomycin A1. Cytosolic alkalinization had no effect on the spreading speed of the Ca2+ signals. The data suggest that the propagation rate of ACh-induced Ca2+ waves is decreased by inhibition of Ca2+ release from intracellular stores due to cytosolic acidification or to Ca2+ pool alkalinization and/or to a decrease in the proton gradient directed from the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool to the cytosol.

scholarly journals Inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate formation in Ca2+-mobilizing-hormone-activated cells

1985 ◽  
Vol 232 (1) ◽  
pp. 237-243 ◽  
Author(s):  
G M Burgess ◽  
J S McKinney ◽  
R F Irvine ◽  
J W Putney
Keyword(s):  
Guinea Pig ◽  
Inositol Trisphosphate ◽  
Acinar Cells ◽  
Temporal Correlation ◽  
Dimethyl Sulphoxide ◽  
Pancreatic Acinar Cells ◽  
Hormone Stimulation ◽  
Inositol 1,4,5 Trisphosphate ◽  
Intracellular Messenger ◽  
Stimulation Of

The inositol trisphosphate liberated on stimulation of guinea-pig hepatocytes, pancreatic acinar cells and dimethyl sulphoxide-differentiated human myelomonocytic HL-60 leukaemia cells is composed of two isomers, the 1,4,5-trisphosphate and the 1,3,4-trisphosphate. Inositol 1,4,5-trisphosphate was released rapidly, with no measurable latency on hormone stimulation, and, consistent with its proposed role as an intracellular messenger for Ca2+ mobilization, there was good temporal correlation between its formation and Ca2+-mediated events in these tissues. There was a definite latency before an increase in the formation of inositol 1,3,4-trisphosphate could be detected. In all of these tissues, however, it formed a substantial proportion of the total inositol trisphosphate by 1 min of stimulation. In guinea-pig hepatocytes, where inositol trisphosphate increases for at least 30 min after hormone application, inositol 1,3,4-trisphosphate made up about 90% of the total inositol trisphosphate by 5-10 min. In pancreatic acinar cells, pretreatment with 20 mM-Li+ caused an increase in hormone-induced inositol trisphosphate accumulation. This increase was accounted for by a rise in inositol 1,3,4-trisphosphate; inositol 1,4,5-trisphosphate was unaffected. This finding is consistent with the observation that Li+ has no effect on Ca2+-mediated responses in these cells. The role, if any, of inositol 1,3,4-trisphosphate in cellular function is unknown.

scholarly journals Ca2+-sensitivity of inositol 1,4,5-trisphosphate-mediated Ca2+ release in permeabilized pancreatic acinar cells

1990 ◽  
Vol 265 (3) ◽  
pp. 681-687 ◽  
Author(s):  
P H G M Willems ◽  
M D De Jong ◽  
J J H H M De Pont ◽  
C H Van Os
Keyword(s):  
Acinar Cells ◽  
Inhibitory Effect ◽  
Feedback Mechanism ◽  
Pancreatic Acinar Cells ◽  
Release Mechanism ◽  
Concomitant Increase ◽  
Permeabilized Cells ◽  
Negative Feedback Mechanism ◽  
Inositol 1,4,5 Trisphosphate ◽  
Energy Dependent

Hormonal and phorbol ester pretreatment of pancreatic acinar cells markedly decreases the Ins(1,4,5)P3-induced release of actively stored Ca2+ [Willems, Van Den Broek, Van Os & De Pont (1989) J. Biol. Chem. 264, 9762-9767]. Inhibition occurred at an ambient free Ca2+ concentration of 0.1 microM, suggesting a receptor-mediated increase in Ca2(+)-sensitivity of the Ins(1,4,5)P3-operated Ca2+ channel. To test this hypothesis, the Ca2(+)-dependence of Ins(1,4,5)P3-induced Ca2+ release was investigated. In the presence of 0.2 microM free Ca2+, permeabilized cells accumulated 0.9 nmol of Ca2+/mg of acinar protein in an energy-dependent pool. Uptake into this pool increased 2.2- and 3.3-fold with 1.0 and 2.0 microM free Ca2+ respectively. At 0.2, 1.0 and 2.0 microM free Ca2+, Ins(1,4,5)P3 maximally released 0.53 (56%), 0.90 (44%) and 0.62 (20%) nmol of Ca2+/mg of acinar protein respectively. Corresponding half-maximal stimulatory Ins(1,4,5)P3 concentrations were calculated to be 0.5, 0.6 and 1.4 microM, suggesting that the affinity of Ins(1,4,5)P3 for its receptor decreases beyond 1.0 microM free Ca2+. The possibility that an inhibitory effect of sub-micromolar Ca2+ is being masked by the concomitant increase in size of the releasable store is excluded, since Ca2+ release from cells loaded in the presence of 0.1 or 0.2 microM free Ca2+ and stimulated at higher ambient free Ca2+ was not inhibited below 1.0 microM free Ca2+. At 2.0 and 10.0 microM free Ca2+, Ca2+, Ca2+ release was inhibited by approx. 30% and 75% respectively. The results presented show that hormonal pretreatment does not lead to an increase in Ca2(+)-sensitivity of the release mechanism. Such an increase in Ca2(+)-sensitivity to sub-micromolar Ca2+ is required to explain sub-micromolar oscillatory changes in cytosolic free Ca2+ by a Ca2(+)-dependent negative-feedback mechanism.

scholarly journals Agonist-dependent Phosphorylation of the Inositol 1,4,5-Trisphosphate Receptor

1999 ◽  
Vol 113 (6) ◽  
pp. 851-872 ◽  
Author(s):  
Andrew P. LeBeau ◽  
David I. Yule ◽  
Guy E. Groblewski ◽  
James Sneyd
Keyword(s):  
Acinar Cells ◽  
Calcium Oscillations ◽  
Pancreatic Acinar Cells ◽  
Ip3 Receptors ◽  
Ip3 Receptor ◽  
Open Probability ◽  
Probability Curve ◽  
Long Period ◽  
Inositol 1,4,5 Trisphosphate ◽  
S Period

The properties of inositol 1,4,5-trisphosphate (IP3)-dependent intracellular calcium oscillations in pancreatic acinar cells depend crucially on the agonist used to stimulate them. Acetylcholine or carbachol (CCh) cause high-frequency (10–12-s period) calcium oscillations that are superimposed on a raised baseline, while cholecystokinin (CCK) causes long-period (>100-s period) baseline spiking. We show that physiological concentrations of CCK induce rapid phosphorylation of the IP3 receptor, which is not true of physiological concentrations of CCh. Based on this and other experimental data, we construct a mathematical model of agonist-specific intracellular calcium oscillations in pancreatic acinar cells. Model simulations agree with previous experimental work on the rates of activation and inactivation of the IP3 receptor by calcium (DuFour, J.-F., I.M. Arias, and T.J. Turner. 1997. J. Biol. Chem. 272:2675–2681), and reproduce both short-period, raised baseline oscillations, and long-period baseline spiking. The steady state open probability curve of the model IP3 receptor is an increasing function of calcium concentration, as found for type-III IP3 receptors by Hagar et al. (Hagar, R.E., A.D. Burgstahler, M.H. Nathanson, and B.E. Ehrlich. 1998. Nature. 396:81–84). We use the model to predict the effect of the removal of external calcium, and this prediction is confirmed experimentally. We also predict that, for type-III IP3 receptors, the steady state open probability curve will shift to lower calcium concentrations as the background IP3 concentration increases. We conclude that the differences between CCh- and CCK-induced calcium oscillations in pancreatic acinar cells can be explained by two principal mechanisms: (a) CCK causes more phosphorylation of the IP3 receptor than does CCh, and the phosphorylated receptor cannot pass calcium current; and (b) the rate of calcium ATPase pumping and the rate of calcium influx from the outside the cell are greater in the presence of CCh than in the presence of CCK.

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