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

Abstract

In pancreatic acinar cells hormonal stimulation leads to a cytosolic Ca2+ 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 [Ca2+] of intracellular stores. We show here that Ca2+ 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 (EC50 = 89 nM) than those at the basolateral side (EC50 = 256 nM). In contrast, cADP-ribose, a modifier of Ca2+-induced Ca2+ release, and nicotinic acid adenine dinucleotide phosphate (NAADP) were able to release Ca2+ exclusively from intracellular stores located at the basolateral cell side. Our data agree with observations that upon stimulation Ca2+ 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 Ca2+ wave propagation from the apical to the basolateral cell side observed in pancreatic acinar cells Ca2+-induced Ca2+ release, modulated by cADP-ribose and/or NAADP, might be involved.