Inositol trisphosphate and cyclic ADP-ribose-mediated release of Ca2+ from single isolated pancreatic zymogen granules

• Published in: Cell 1996-02, Vol.84 (3), p.473-480
• Main Authors: Gerasimenko, O V, Gerasimenko, J V, Belan, P V, Petersen, O H
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate Ribose - analogs & derivatives; Adenosine Diphosphate Ribose - metabolism; Adenosine Diphosphate Ribose - pharmacology; Animals; Calcium - metabolism; Cyclic ADP-Ribose; Cytoplasmic Granules - drug effects; Cytoplasmic Granules - metabolism; Enzyme Precursors - metabolism; In Vitro Techniques; Inositol 1,4,5-Trisphosphate - metabolism; Inositol 1,4,5-Trisphosphate - pharmacology; Mice; Microscopy, Confocal; Pancreas - drug effects; Pancreas - metabolism; Pancreas - ultrastructure
• ISSN: 0092-8674
• DOI: 10.1016/s0092-8674(00)81292-1

In pancreatic acinar cells low (physiological) agonist concentrations evoke cytosolic Ca2+ spikes specifically in the apical secretory pole that contains a high density of secretory (zymogen) granules (ZGs). Inositol 1,4,5-trisphosphate (IP3) is believed to release Ca2+ from the endoplasmic reticulum, but we have now tested whether the Ca(2+)-releasing messengers IP3 and cyclic ADP-ribose (cADPr) can liberate Ca2+ from AGs. In experiments on single isolated ZGs, we show using confocal microscopy that IP3 and cADPr evoke a marked decrease in the free intragranular Ca2+ concentration. Using a novel high resolution method, we have measured changes in the Ca2+ concentration in the vicinity of an isolated AG and show that IP3 and cADPr cause rapid Ca2+ release from the granule, explaining the agonist-evoked cytosolic Ca2+ rise in the secretory pole.