"We found that application of cholecystokinin to isolated populations of pancreatic acinar cells caused NAAPD level to increase as much as 6-fold in only 5 to 10 seconds," Yamasaki said. The cholecystokinin-A receptor, expressed predominantly in pancreatic acinar cells, has two binding sites, one of high and one of low affinity.
"Unequivocal evidence that NAADP is a crucial messenger"
"Intriguingly, the plot of NAADP level versus cholecystokinin concentration was best fit with a two-site model, suggesting that both the high- and low-affinity sites were linked to NAADP production," Yamasaki said. In contrast to the hormone cholecystokinin, the neurotransmitter acetylcholine failed to affect NAADP level, even when applied at supramaximal concentrations in terms of physiological relevance and which saturate the calcium amplitude and spiking frequency.
In conclusion, Yamasaki said, "Our data in this experiment provides the first direct evidence that cholecystokinin elicits a rapid, dose-dependent and selective increase in NAADP, and thus unequivocal evidence that NAADP is a crucial messenger employed by cholecystokinin."
Yamasaki noted that NAADP has "a short history compared to other traditional intracellular messengers and many aspects of this molecule remain under investigation. However the potential of this new messenger as a therapeutic target should not be underestimated," she added.