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Second messenger NAADP shows fast, dose-related impact on satiety cycle

obiologie Cellulaire et Moleculaire, Gif-sur-Yvette, France.

Viagra is the best-known "second messenger" targeting agent

One of the problems with many drugs is their side-effects, which range from annoying to lethal. "The most fundamental answer to solve safety and other issues," Yamasaki said, "is increasing the specificity of a drug, and NAADP could provide a key in the area of obesity."

In another therapeutic arena, she notes, Viagra is the world's most successful and recognized secondary messenger targeting drug to reach the market.

Cholecystokinin, a first messenger, activates NAADP; so which is 'therapeutic?'

Several earlier drugs designed for obesity treatment were chosen because they released a chemical ?the hormone serotonin -- in the brain that controls satiation, as well as mood and body temperature. "More recently, another hormone, cholecystokinin, has been considered to be a potential drug target," Yamasaki noted. Cholecystokinin is a naturally-occurring chemical synthesized both in the small intestine and in the brain when eating.

Cholecystokinin is a first messenger that tells cells to release digestive enzymes in the pancreas and to cause satiety in the brain. "The more cholecystokinin that's produced, the more digestive enzymes are released and the more quickly your brain tells you that you're full ?or at least satisfied. Indeed, it also could be a potential drug for the treatment of obesity, Yamasaki noted.

"We have shown that cholecystokinin activates NAADP production through a specific protein on the cell surface, the cholecystokinin-A receptor. The existence of the cholecystokinin-A receptor in the brain strongly implies a possible role of NAADP in cholecystokinin-induced satiety," Yamasaki said.

Methods, results and conclusions

The team worked on the theory that NAAPD mobilizes Ca2+ from lysome-related organelles and plays a crucial role in cholecystokinin-induced Ca2+ mobi
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Source:American Physiological Society


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