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

Cell. 1996 Feb 9;84(3):473-80. doi: 10.1016/s0092-8674(00)81292-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Enzyme Precursors
  • Cyclic ADP-Ribose
  • Adenosine Diphosphate Ribose
  • Inositol 1,4,5-Trisphosphate
  • Calcium