THE CYCLIC ADP RIBOSE ANTAGONIST 8-NH2-CADP-RIBOSE BLOCKS CHOLECYSTOKININ-EVOKED CYTOSOLIC CA2-CELLS( SPIKING IN PANCREATIC ACINAR)

In order to investigate the possible involvement of cyclic ADP ribose as all intracellular messenger for hormone-evoked cytosolic Ca2+ signa lling, we performed experiments on intracellularly perfused mouse panc reatic acinar cells. Both a stable inositol 1,4,5 trisphosphate analog ue (IP3) and cyclic ADP ribose (cADPR) evoked regular spikes of Ca2+ d ependent 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 cholecystoki nin (CCK) in a physiological concentration (2.5-5 pM) evoked a mixture of short-lasting and longer-lasting spikes of Ca2+-dependent ion curr ent, 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 experiment s provide fresh evidence for the involvement of cADPR receptors in the hormone-evoked cytosolic Ca2+ signalling process in pancreatic acinar cells.