Pancreatic acinar cells (PAC) are secretory cells responsible for the synthesis of many digestive enzymes, the pathological activation of which can result in the inflammatory disease acute pancreatitis (AP). This non-physiological activation has been linked to toxic levels of [Ca2+]i, which can be induced by various agents including bile acids, e.g. Taurolithocholic-acid-3-sulfate (TLC-S) and Sodium Cholate (NaChol). While TLC-S induced [Ca2+]i increases are known to involve a nicotinic acid adenine dinucleotide phosphate (NAADP) dependent component1, this is unknown for NaChol. Wild type and knockout mice of the NAADP receptor TPCN22, sacrificed humanly using a schedule 1 approved method, were used to create preparations of PAC. The effects of two NAADP antagonists (Ned-193 and BZ1944) and GSK-7975A5 (a Ca2+ release-activated Ca2+ channel blocker) were tested on these preparations using fluorescent Ca2+ imaging and a necrosis/apoptosis assay. PAC synthesise NAADP in response to Cholecystokinin (CCK); Ned-19 but not BZ194 showed the ability to inhibit [Ca2+]i oscillations induced by physiological concentrations of CCK. ACh induced oscillations are NAADP independent and showed no sensitivity to Ned-19. Ned-19 also showed the ability to partially inhibit TLC-S induced [Ca2+]i increases. BZ194 had no effect on the levels of necrosis induced by TLC-S; while Ned-19 and GSK-7975A both caused reductions in necrosis induced by both TLC-S and NaChol. No significant difference was observed in the levels of TLC-S induced necrosis in TPCN2 KO mice and wild types, though Ned-19 also displayed a protective effect in the KO mice. These results show that the NAADP antagonist Ned-19, but not BZ194, possibly in combination with GSK-7975A, might provide a pharmacological approach to managing AP.