Cell side-specific sensitivities of intracellular Ca2+ stores for inositol 1,4,5-trisphosphate, cyclic ADP-ribose, and nicotinic acid adenine dinucleotide phosphate in permeabilized pancreatic acinar cells from mouse

J Biol Chem. 2002 Apr 5;277(14):11696-702. doi: 10.1074/jbc.M107794200. Epub 2002 Jan 23.

Abstract

In pancreatic acinar cells hormonal stimulation leads to a cytosolic Ca(2+) wave that starts in the apical cell pole and subsequently propagates toward the basal cell side. We used permeabilized pancreatic acinar cells from mouse and the mag-fura-2 technique, which allows direct monitoring of changes in [Ca(2+)] of intracellular stores. We show here that Ca(2+) can be released from stores in all cellular regions by inositol 1,4,5-trisphosphate. Stores at the apical cell pole showed a higher affinity to inositol 1,4,5-trisphosphate (EC(50) = 89 nm) than those at the basolateral side (EC(50) = 256 nm). In contrast, cADP-ribose, a modifier of Ca(2+)-induced Ca(2+) release, and nicotinic acid adenine dinucleotide phosphate (NAADP) were able to release Ca(2+) exclusively from intracellular stores located at the basolateral cell side. Our data agree with observations that upon stimulation Ca(2+) is released initially at the apical cell side and that this is caused by high affinity inositol 1,4,5-trisphosphate receptors. Moreover, our findings allow the conclusion that in Ca(2+) wave propagation from the apical to the basolateral cell side observed in pancreatic acinar cells Ca(2+)-induced Ca(2+) release, modulated by cADP-ribose and/or NAADP, might be involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / analogs & derivatives*
  • Adenosine Diphosphate Ribose / chemistry*
  • Adenosine Diphosphate Ribose / metabolism*
  • Animals
  • Calcium / metabolism*
  • Cell Membrane / metabolism
  • Cyclic ADP-Ribose
  • Cytoplasm / metabolism
  • Dose-Response Relationship, Drug
  • Fluorescent Dyes / pharmacology
  • Fura-2 / pharmacology
  • Heparin / pharmacology
  • Inositol 1,4,5-Trisphosphate / chemistry*
  • Mice
  • Microscopy, Confocal
  • Models, Biological
  • NADP / analogs & derivatives*
  • NADP / chemistry*
  • NADP / metabolism
  • Pancreas / cytology*
  • Protein Binding

Substances

  • Fluorescent Dyes
  • Cyclic ADP-Ribose
  • Adenosine Diphosphate Ribose
  • NADP
  • NAADP
  • Inositol 1,4,5-Trisphosphate
  • Heparin
  • Calcium
  • Fura-2