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). 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.
Gerasimenko
O V
OV
Medical Research Council Secretory Control, Physiological Laboratory, University of Liverpool, United Kingdom.
Gerasimenko
J V
JV
Belan
P V
PV
Petersen
O H
OH
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D036563:Cyclic ADP-Ribose; D003594:Cytoplasmic Granules / Q000187:drug effects* / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D018613:Microscopy, Confocal; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure
D004792:Enzyme Precursors; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium