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Bile acids induce calcium signals in mouse pancreatic acinar cells: implications for bile-induced pancreatic pathology - PubMed

  • ️Tue Jan 01 2002

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

Svetlana Voronina et al. J Physiol. 2002.

Abstract

The effect of the natural bile acid, taurolithocholic acid 3-sulfate (TLC-S), on calcium signalling in pancreatic acinar cells has been investigated. TLC-S induced global calcium oscillations and extended calcium transients as well as calcium signals localised to the secretory granule (apical) region of acinar cells. These calcium signals could still be triggered by TLC-S in a calcium-free external solution. TLC-S-induced calcium signals were not inhibited by atropine, but were abolished by caffeine or by depletion of calcium stores, due to prolonged application of ACh. Global calcium signals, produced by TLC-S application, displayed vectorial apical-to-basal polarity. The signals originated in the apical part and were then propagated to the basal region. Other natural bile acids, taurocholate (TC) and taurodeoxycholate (TDC), were also able to produce local and global calcium oscillations (but at higher concentrations than TLC-S). Bile, which can enter pancreas by reflux, has been implicated in the pathology of acute pancreatitis. The calcium releasing properties of bile acids suggest that calcium toxicity could be an important contributing factor in the bile acid-induced cellular damage.

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Figures

Figure 1
Figure 1. TLC-S induces calcium signals in pancreatic acinar cells due to calcium release from internal stores

A, patterns of calcium responses induced by 100 μ

m

TLC-S in three individual cells (shown by different colours) from the same acinar triplet. B, calcium responses to TLC-S (200 μ

m

) in calcium-free external solution. C, prolonged TLC-S-induced calcium transients were acutely sensitive to removal of calcium from the extracellular solution. The TLC-S concentration was 500 μ

m

.

Figure 2
Figure 2. Comparison of ACh- and TLC-S-mediated calcium release

A, atropine (100 μ

m

) had no effect on TLC-S (200 μ

m

)-induced release of calcium. B, caffeine (20 m

m

) blocked the TLC-S-induced response. The TLC-S concentration was 200 μ

m

. Removal of caffeine unmasked the effect of TLC-S. The two traces represent two cells from the same acinar doublet. In this experiment, cells were loaded with Fura Red (unlike other experiments, shown in this and other figures, where Fluo 4 was used as a calcium indicator). The fluorescence of Fura Red is only slightly affected by caffeine. Decrease of Fura Red fluorescence corresponds to an increase in the calcium concentration (please note the changes in the scale for this part of the figure). C, ACh (10 μ

m

) stimulation is able to completely discharge the TLC-S-sensitive calcium store. The TLC-S concentration was 200 μ

m

.

Figure 3
Figure 3. Local apical calcium responses induced by TLC-S and apical origin of global TLC-S responses

The colour of the traces corresponds to the colour of the regions indicated on the transmitted light pictures. Aa, the transmitted light image of the pancreatic acinar triplet and the regions of interest from which the fluorescence was collected. The red trace (Ab) and the red circle (Aa) correspond to the secretory granule region (apical part), the blue colour represents the basal region (Aa,b). Ba, the transmitted light image. The traces shown in Bc were recorded from regions indicated by circles on the transmitted light image. Bb, whole cell response from the top cell in the image. Bc, fluorescence changes in the regions of interest: red trace corresponds to apical region; green trace represents measurements taken from the central part of the cell; blue trace was recorded from the basal region.

Figure 4
Figure 4. Local and global responses induced by TC and TDC

The colour of the traces corresponds to the colour of the regions indicated on the transmitted light pictures. A, effect of TC. Regions of interests from which measurements were taken are indicated by circles on transmitted light image (Aa). Ab, local (e.g. transients 1, 2, 4, 5…) and global (transients 3 and 6) calcium responses induced by TC. B, effect of TDC. Regions of interests from which measurements were taken are indicated on the transmitted light image (Ba). Bb, global (first transient) and local (transients 2 and 3) calcium responses induced by TDC.

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References

    1. Anwer MS, Engelking LR, Nolan K, Sullivan D, Zimniak P, Lester R. Hepatotoxic bile acids increase cytosolic Ca2+ activity of isolated rat hepatocytes. Hepatology. 1988;8:887–891. - PubMed
    1. Bolender RP. Stereological analysis of the guinea pig pancreas. I. Analytical model and quantitative description of nonstimulated pancreatic exocrine cells. Journal of Cell Biology. 1974;61:269–287. - PMC - PubMed
    1. Bouscarel B, Kroll SD, Fromm H. Signal transduction and hepatocellular bile acid transport: cross talk between bile acids and second messengers. Gastroenterology. 1999;117:433–452. - PubMed
    1. Cancela JM, Gerasimenko OV, Gerasimenko JV, Tepikin AV, Petersen OH. Two different but converging messenger pathways to intracellular Ca2+ release: the roles of nicotinic acid adenine dinucleotide phosphate, cyclic ADP-ribose and inositol trisphosphate. EMBO Journal. 2000;19:2549–2557. - PMC - PubMed
    1. Capiod T, Combettes L, Noel J, Claret M. Evidence for bile acid-evoked oscillations of Ca2+-dependent K+ permeability unrelated to a D-myo-inositol 1,4,5-trisphosphate effect in isolated guinea pig liver cells. Journal of Biological Chemistry. 1991;266:268–273. - PubMed

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