Nicotinic acid adenine dinucleotide phosphate

Nicotinic acid adenine dinucleotide phosphate popularly known as NAADP+ is a nucleotide very similar to NADP differing only in that instead of the nicotinamide there is a niacin moiety. But this small change makes a lot of difference in their cellular function. NAADP is one of the most potent Calcium signaling messenger causing release of calcium from intracellular stores.

Metabolism
Bifunctional ectoenzymes of the CD38 family synthesize NAADP+ from NADP+ (by exchange of nicotinamide for niacin under acidic conditions) and the same enzymes are also capable to hydrolyzing them.

Transport
The two paralogous enzymes- transmembrane CD38 and GPI anchored CD157, that produce NAADP (and cADPR) in humans both have their active synthesis site in the ectodomain. Though this may involve vesicular synthesis but it has been shown that it is produced at the extracellular sites, and also can act when produced by a different cell or added artificially from outside. So the NAADP has to enter the cell either by diffusion or by transport. Considering the fact that the substrate of NAADP synthesis (NADP) itself is very sparse in the extracellular medium, a purse diffusion based mechanism has been suspected to be less likely than a transporter mediated path. This is compatible with recent data which indicate a carrier mediated transport partially blockable by dipyridamole and cold temperature.

Mechanism of action
The real target of NAADP which causes the calcium release is still not clear. There has been some report on a ligand gated calcium release channel present in different distribution compared to both Ryanodine receptors and IP3 receptors. This receptor may be present on both endoplasmic reticulum/nuclear membrane compartments as well as some acidified compartments like lysosome and some secretory vesicles. Some report also suggest that NAADP may act on Ryanodine receptor as well.

An unique feature of NAADP action is its desensitization on prolonged action even when at subthreshold concentration. This is supposed to be a part of calcium memory of cellular calcium signaling pathways.