Bombesin-induced cytosolic Ca2+ spiking in pancreatic acinar cells dependson 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 a re triggered by activation of acetylcholine (ACh), cholecystokinin (CCK) an d bombesin receptors. Low concentrations of these three agonists all induce local Ca2+ spikes, but in the case of bombesin and CCK these spikes can al so 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 inhibit ed by ryanodine (50 muM). We then demonstrate that, like CCK- but unlike AC h-induced oscillations, the responses to bombesin are abolished by intracel lular infusion of the cyclic ADP ribose (cADPr) antagonist 8-NH2-cADPr (20 muM). We conclude that in mouse pancreatic acinar cells, bombesin, CCK and ACh all produce local Ca2+ spikes by recruiting common oscillator units com posed 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. (C) 2001 Ha rcourt Publishers Ltd.