Yamasaki et al., "The ecto-enzyme CD38 is a nicotinic acid adenine dinucleotide phosphate (NAADP
) synthase that couples receptor activation to [Ca.sup.2+] mobilization from lysosomes in pancreatic acinar cells," Journal of Biological Chemistry, vol.
Cyclic ADP-ribose and NAADP
: Fraternal twin messengers for calcium signaling.
With the aid of Ned-19 in their experiments, the researchers have discovered that NAADP plays a crucial role in insulin secretion, and thus represents a brand new target for diabetes drugs.
But now that we know how important NAADP is we can start to look for drugs that work with NAADP to increase insulin secretion rather than decrease it.
The uptake mechanisms of [Ca.sup.2+] into the cytoplasm refer to the inositol 1,4,5-trisphosphate receptor ([IP.sub.3]R), the ryanodine receptor (RyR), and the nicotinic acid-adenine dinucleotide phosphate (NAADP
) that are responsible for [Ca.sup.2+] release from ER and SR, as well as voltage-dependent [Ca.sup.2+] channels (VDCC) and store-operated [Ca.sup.2+] channel (SOC), which are in charge of [Ca.sup.2+] influx from extracellular matrix [100-102].
CD38 is a multifunctional enzyme capable of synthesizing the second messenger, cADPR, and NAADP
. However, the major enzymatic activity of CD38 is the hydrolysis of [NAD.sup.+] .
CD38 is simultaneously a receptor and adhesion molecule as well as an ectoenzyme that catalyses the synthesis of ADP ribose (ADPR), cyclic ADPR (cAdPR), and nicotinic acid adenine dinucleotide phosphate (NAADP
), starting from nicotinamide adenine dinucleotide ([NAD.sup.+]).