INOSITOL TRISPHOSPHATE AND CYCLIC ADP-RIBOSE-MEDIATED RELEASE OF CA2+FROM SINGLE ISOLATED PANCREATIC ZYMOGEN GRANULES

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). In ositol 1,4,5-trisphosphate (IP3) is believed to release Ca2+ from the endoplasmic reticulum, but we have now tested whether the Ca2+-releasi ng messengers IP3 and cyclic ADP-ribose (cADPr) can liberate Ca2+ from ZGs. In experiments on single isolated ZGs, we show using confocal mi croscopy that IP3 and cADPr evoke a marked decrease in the free intrag ranular Ca2+ concentration. Using a novel high resolution method, we h ave measured changes in the Ca2+ concentration in the vicinity of an i solated ZG and show that IP3 and cADPr cause rapid Ca2+ release from t he granule, explaining the agonist-evoked cytosolic Ca2+ rise in the s ecretory pole.