Agonist-stimulated pathways of calcium signaling in pancreatic acinar cells

In pancreatic acinar cells stimulation of different intracellular pathways leads to different patterns of Ca2+ signaling, Bombesin induces activation of both phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) and phospholipase D (PLD), The latter leads to generation of diacy lglycerol (DAG) in addition to that produced by activation of PIP2-PLC. Str ong activation of protein kinase C (PKC) results in inhibition of Ca2+-indu ced Ca2+ release from Ca2+ pools arranged in sequence to the luminally loca ted IP3-sensitive Ca2+ pools. Consequently the Ca2+ wave which starts in th e luminal cell pole is slower in the presence of bombesin (5 mu m/s) as com pared to that in the presence of acetylcholine (17 mu m/s) which activates PIP2-PLC but not PLD, Activation of high-affinity CCK-receptors triggers a Ca2+ wave with slow propagation (5 mu m/s) due to stimulation of phospholip ase A(2) (PLA(2)) and generation of arachidonic acid, which in turn leads t o inhibition of Ca2+-induced Ca2+ release. Low-affinity CCK-receptors are c oupled to both PIP2-PLC and PLD.