IP3 and cyclic ADP-ribose induced Ca2+ release from intracellular stores of pancreatic acinar cells from rat in primary culture

We have measured Ca2+ concentration changes in intracellular Ca2+ stores ([ Ca2+](store)) of rat pancreatic acinar cells in primary culture in response to the Ca2+ mobilizing substances inositol-1,4,5-trisphosphate (IP3) and c yclic ADP-ribose (cADPr) using the Ca2+-sensitive dye mag Fura-2. We found that in this cell model IP3 releases Ca2+ in a quantal manner. Higher Ca2concentration in the stores allowed a response to lower IP3 concentrations ([IP3]) indicating that the sensitivity of IP3 receptors to IP3 is regulate d by the Ca2+ concentration in the stores. Cyclic ADPr, that modifies 'Ca2-induced-Ca2+-release' (CICR), was also able to release Ca2+ from intracell ular stores of pancreatic acinar cells in primary culture. In comparison to the Ca2+ ionophore ionomycin, which induced a maximal decrease (100%) in [ Ca2+](store), a hypermaximal [IP3] (10 muM) dropped [Ca2+](store) by 87% an d cADPr had no further effect. Cyclic ADPr reduced [Ca2+](store) by only 56 % and subsequent IP3 addition caused further maximal decrease in [Ca2+](sto re). Furthermore, a maximal [IP3] caused the same decrease in [Ca2+](store) in all regions of the cell, whereas cADPr dropped the [Ca2+](store) betwee n 20 and 80% in different cell regions. From these data we conclude that in primary cultured rat pancreatic acinar cells at least three types of Ca2stores exist. One type possessing both cADPr receptors and IP3 receptors, a second type possessing only IP3 receptors, and a third type whose Ca2+ can be released by ionomycin but neither by IP3 nor by cADPr. (C) 2001 Harcour t Publishers Ltd.