NAADP signaling revisited

Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca²⁺ mobilizing endogenous compound known to date. Although its Ca²⁺ releasing activity has been demonstrated in many cell types and in response to different extracellular stimuli, several aspects of NAADP signaling are unclear. This overview focuses on the controversial aspects and reviews NAADP's role as second messenger: endogenous concentrations and its receptor-mediated alterations, metabolism, and potential organelle and ion channel targets. Finally, the role of NAADP as Ca²⁺ trigger is discussed by reviewing the development of local into global Ca²⁺ signals evoked by NAADP.