Bombesin-induced cytosolic Ca2+spiking in pancreatic acinar cells depends on cyclic ADP-ribose and ryanodine receptors

Different hormones and neurotransmitters, using Ca2+as their intracellular messenger, can generate specific cytosolic Ca2+signals in different parts of a cell. In mouse pancreatic acinar cells, cytosolic Ca2+oscillations are triggered by activation of acetylcholine (ACh), cholecystokinin (CCK) and bombesin receptors. Low concentrations of these three agonists all induce local Ca2+spikes, but in the case of bombesin and CCK these spikes can also trigger global Ca2+signals. Here we monitor cytosolic Ca2+oscillations induced by low (2–5 pM) concentrations of bombesin and show that, like ACh- and CCK-induced oscillations, the bombesin-elicited responses are inhibited by ryanodine(50μM). We then demonstrate that, like CCK- but unlike ACh-induced oscillations, the responses to bombesin are abolished by intracellular infusion of the cyclic ADP ribose (cADPr) antagonist 8-NH2-cADPr (20μM). We conclude that in mouse pancreatic acinar cells, bombesin, CCK and ACh all produce local Ca2+spikes by recruiting common oscillator units composed of ryanodine and inositol trisphosphate receptors. However, bombesin and CCK also recruit cADPr receptors, which may account for the global Ca2+signals that can be evoked by these two agonists. Our new results indicate that each Ca2+-mobilizing agonist, acting on mouse pancreatic acinar cells, recruits a unique combination of intracellular Ca2+channels