We have shown that all intracellular Ca2+ messengers NAADP, cADPR or IP3 can all induce Ca2+ release from both thapsigargin-sensitive and insensitive intracellular stores. Even after complete depletion of the ER store by thapsigargin, NAADP, IP3 or cADPR can release Ca2+ from acidic stores located exclusively in the secretory granule region. Ryanodine or Ruthenium Red blocks the NAADP-induced as well as the cADPR-elicited Ca2+ release, suggesting that both NAADP and cADPR activate ryanodine receptors. Pancreatic acinar cells possess two types of distinct Ca2+ stores: the thapsigargin-sensitive ER and an acidic thapsigargin-insensitive compartment in the apical secretory granule region. In both these stores the ryanodine receptors can be activated by either NAADP or cADPR and the IP3 receptors by IP3.

Recently we have also shown that application of pathological agents such as bile acids or menadione induce cytosolic calcium rise, and release calcium from both thapsigargin-sensitive ER store, and from thapsigargin-insensitive acidic calcium store. We conclude that all intracellular Ca2+ stores thapsigargin-sensitive (ER) and thapsigargin-insensitive (acidic) Ca2+ stores actively participate in both physiological and pathological calcium signalling.