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

Abstract

 In order to investigate the possible involvement of cyclic ADP ribose as an 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 μM). Increasing the CCK concentration to 15 pM could overcome the inhibition by 18 μM 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.