Specific Ca2+ signaling evoked by cholecystokinin and acetylcholine: The roles of NAADP, cADPR, and IP3

In order to control cell functions, hormones and neurotransmitters gene rat e an amazing diversity of Ca2+ signals such as local and global Ca2+ elevat ions and also Ca2+ oscillations. In pancreatic acinar cells, cholecystokini n (CCK) stimulates secretion of digestive enzyme and promotes cell growth, whereas acetylcholine (ACh) essentially triggers enzyme secretion. Pancreat ic acinar cells are a classic model for the study of CCK- and ACh-evoked sp ecific Ca2+ signals. In addition to inositol 1,4,5 trisphosphate (IP3), rec ent studies have shown that cyclic ADPribose (cADPr) and nicotinic acid ade nine dinucleotide phosphate (NAADP) release Ca2+ in pancreatic acinar cells . Moreover, it has also been shown that both ACh and CCK trigger Ca2+ spike s by co-activation of IP3 and ryanodine receptors but by different means. A Ch uses IP3 and Ca2+, whereas CCK uses cADPr and NAADP. In addition, CCK ac tivates phospholipase A(2) and D. The concept emerging from these studies i s that agonist specific Ca2+ signals in a single target cell are generated by combination of different intracellular messengers.