Specific Ca²⁺ Signaling Evoked by Cholecystokinin and Acetylcholine: The Roles of NAADP, cADPR, and IP3

In order to control cell functions, hormones and neurotransmitters generate an amazing diversity of Ca²⁺ signals such as local and global Ca²⁺ elevations and also Ca²⁺ oscillations. In pancreatic acinar cells, cholecystokinin (CCK) stimulates secretion of digestive enzyme and promotes cell growth, whereas acetylcholine (ACh) essentially triggers enzyme secretion. Pancreatic acinar cells are a classic model for the study of CCK- and ACh-evoked specific Ca²⁺ signals. In addition to inositol 1,4,5 trisphosphate (IP3), recent studies have shown that cyclic ADPribose (cADPr) and nicotinic acid adenine dinucleotide phosphate (NAADP) release Ca²⁺ in pancreatic acinar cells. Moreover, it has also been shown that both ACh and CCK trigger Ca²⁺ spikes by co-activation of IP3 and ryanodine receptors but by different means. ACh uses IP3 and Ca²⁺, whereas CCK uses cADPr and NAADP. In addition, CCK activates phospholipase A2 and D. The concept emerging from these studies is that agonist-specific Ca²⁺ signals in a single target cell are generated by combination of different intracellular messengers.