The cyclic ADP ribose antagonist 8-NH2-cADP-ribose blocks cholecystokinin-evoked cytosolic Ca2+ spiking in pancreatic acinar cells

In order to investigate the possible involvement of cyclic ADP ribose as all intracellular messenger for hormone-evoked cytosolic Ca2+ signalling, we performed experiments on intracellularly perfused mouse pancreatic acinar cells. Both a stable inositol 1,4,5 trisphosphate analogue (IP3) and cyclic ADP ribose (cADPR) evoked regular spikes of Ca2+ dependent ion current, reflecting cytosolic Ca2+ spiking. The effect of cADPR, but not IP3, was abolished by the presence intracellularly of the cADPR antagonist 8-NH2-cADPR, External application of cholecystokinin (CCK) in a physiological concentration (2.5-5 pM) evoked a mixture of short-lasting and longer-lasting spikes of Ca2+-dependent ion current, These effects were abolished by the presence intracellularly of 8-NH2-cADPR (18 mu M). Increasing the CCK concentration to 15 pM could overcome the inhibition by 18 mu M of the antagonist. These experiments provide fresh evidence for the involvement of cADPR receptors in the hormone-evoked cytosolic Ca2+ signalling process in pancreatic acinar cells.