Acute pancreatitis (AP) is a potentially fatal condition caused by non-physiological activation of the digestive enzymes within pancreatic acinar cells (PAC), resulting in an inflammation of the pancreas and surrounding tissue. Various pathological agents, including the bile acid Taurolithocholic-acid-3-sulfate (TLC-S), produce toxic levels of [Ca2+]i in PAC and induce AP1. TLC-S induced [Ca2+]i increases in PAC have been shown to have a nicotinic acid adenine dinucleotide phosphate (NAADP) dependent component2. We tested the effects of the NAADP antagonist Ned-193 on TLC-S induced Ca2+ signalling in PAC preparations using Ca2+ imaging and a necrosis/apoptosis assay. Preparations were made from wild type and knockouts mice of the NAADP receptor TPCN24, which were sacrificed humanly using a schedule 1 approved method. Additionally the protective ability of the Ca2+ release-activated Ca2+ channels (CRAC) blocker GSK-7975A, which has been shown to protect against AP inducing agent Palmitoleic Acid ethyl ester5, was tested against TLC-S. [Ca2+]i oscillations induced by physiological concentrations of cholecystokinin (CCK), which signals via NAADP, were completely abolished by Ned-19. ACh induced oscillations, which are NAADP independent, show no sensitivity to Ned-19. A partial inhibition of the [Ca2+]i increase induced by TLC-S was observed in the presence of Ned-19. Both Ned-19 and GSK-7975A showed the ability to reduce the amount of necrosis induced by either TLC-S or another bile acid, Sodium Cholate. These results show that Ned-19, possibly in combination with GSK-7975A, might provide a pharmacological approach to managing AP.