Cyclic ADP-ribose regulation of ryanodine receptors involved in agonist evoked cytosolic Ca2+ oscillations in pancreatic acinar cells

EMBO J. 1994 May 1;13(9):2038-43. doi: 10.1002/j.1460-2075.1994.tb06478.x.


We have investigated the role of the ryanodine-sensitive intracellular Ca2+ release channel (ryanodine receptor) in the cytosolic Ca2+ oscillations evoked in pancreatic acinar cells by acetylcholine (ACh) or cholecystokinin (CCK). Ryanodine abolished or markedly inhibited the agonist evoked Ca2+ spiking, but enhanced the frequency of spikes evoked by direct internal inositol trisphosphate (InsP3) application. We have also investigated the possibility that cyclic ADP-ribose (cADP-ribose), the putative second messenger controlling the ryanodine receptor, plays a role in Ca2+ oscillations. We found that cADP-ribose could itself induce repetitive Ca2+ spikes localized in the secretory pole and that these spikes were blocked by ryanodine, but also by the InsP3 receptor antagonist heparin. Our results indicate that both the ryanodine and the InsP3 receptors are involved in Ca2+ spike generation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adenosine Diphosphate Ribose / analogs & derivatives*
  • Adenosine Diphosphate Ribose / metabolism
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Cholecystokinin / pharmacology
  • Cyclic ADP-Ribose
  • Cytosol / metabolism
  • Evoked Potentials / drug effects
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Heparin / pharmacology
  • Inositol 1,4,5-Trisphosphate / pharmacology
  • Muscle Proteins / metabolism*
  • Pancreas / cytology
  • Pancreas / drug effects
  • Pancreas / metabolism*
  • Ruthenium Red / pharmacology
  • Ryanodine / pharmacology
  • Ryanodine Receptor Calcium Release Channel


  • Calcium Channels
  • Muscle Proteins
  • Ryanodine Receptor Calcium Release Channel
  • Ruthenium Red
  • Cyclic ADP-Ribose
  • Ryanodine
  • Adenosine Diphosphate Ribose
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Caffeine
  • Inositol 1,4,5-Trisphosphate
  • Heparin
  • Cholecystokinin
  • Acetylcholine
  • Calcium