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

One traditional approach to pharmaceutical design uses so-called "first messengers" ?hormones, other natural facilitators or synthetic products ?to initiate various cellular cascades for the desired physiological effect. To date, despite concerted efforts at all levels of research, this approach has failed to develop a truly successful obesity drug to address this major global health problem.

Enter a recently discovered and already controversial natural molecule called nicotinic acid adenine dinucleotide phosphate (NAADP), which is active in cells from plants to humans. NAADP is thought to be a so-called "second messenger," because it works from inside cells, rather than externally. However its mode operation remains unknown ?and controversial in several aspects.

Results of a new study "establishes NAADP as a new second messenger, and the study of this novel molecule has potential to extend its clinical significance, possibly as a candidate for treating obesity," according to the lead author, Michiko Yamasaki at the Department of Pharmacology, University of Oxford, United Kingdom.

Yamasaki is presenting the research at the 35th Congress of the International Union of Physiological Sciences in San Diego, March 31 - April 5, 2005.

*Paper presentation and "controversy" appearance: "Rapid, selective and dose-dependent elevation of the second messenger NAADP," 12:30 p.m.-3 p.m. Tuesday April 5, Physiology 932.3/board #A438. On view 7:30 a.m. - 4 p.m.

In addition, Ms. Yamasaki was chosen to participate in a special "controversy" session #654 of the Calcium Signaling Track on April 4 in room 29C of the Convention Center beginning at 10:30; her presentation is scheduled for 11:45 a.m.

The team working on the study was comprised of Michiko Yamasaki, Grant Churchill and Antony Galione at the Department of Pharmacology, University of Oxford; Sandip Patel at University College London; and Jose M. Cancela at CNRS, Laboratoire de Neur 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 lization in pancreatic acinar cells. Despite the intensive study into the physiological role of NAADP in Ca2+ signaling in pancreatic anicar cells, direct demonstration of changes in NAADP levels in response to agonist-stimulations has been lacking, Yamasaki said.

"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.


'"/>

Source:American Physiological Society


Related biology news :

1. Second opinion yields treatment changes for half of patients
2. Molecular messengers perform a crucial role in the ability of injured nerve cells to heal themselves
3. Killing the messenger RNA -- But which one?
4. Notorious cancer gene may work by destroying messenger
5. Genome of deadly amoeba shows surprising complexity, evidence of lateral gene transfer
6. “Nano-scissors?laser shows precise surgical capability
7. Clam embryo study shows pollutant mixture adversely affects nerve cell development
8. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
9. Study shows nanoshells ideal as chemical nanosensors
10. Gene vaccine for Alzheimers disease shows promising results
11. Flocking together: Study shows how animal groups find their way
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/31/2016)... R.I. , March 31, 2016  Genomics firm ... of founding CEO, Barrett Bready , M.D., who ... members of the original technical leadership team, including Chief ... President of Product Development, Steve Nurnberg and Vice President ... returned to the company. Dr. Bready served ...
(Date:3/23/2016)... March 23, 2016 ... Sicherheit Gesichts- und Stimmerkennung mit Passwörtern ... (NASDAQ: MESG ), ein führender Anbieter ... Unternehmen mit SpeechPro zusammenarbeitet, um erstmals dessen ... wird die Möglichkeit angeboten, im Rahmen mobiler ...
(Date:3/22/2016)... Ontario , PROVO and ... Newborn Screening Ontario (NSO), which operates the ... for molecular testing, and Tute Genomics and UNIConnect, ... management technology respectively, today announced the launch of a ... next-generation sequencing (NGS) testing panel. NSO ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... While the majority of commercial spectrophotometers and fluorometers ... the 6000i models are higher end machines that use the more unconventional z-dimension of ... beam from the bottom of the cuvette holder. , FireflySci has developed several ...
(Date:6/23/2016)... 2016 /PRNewswire/ - FACIT has announced the creation ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or "the ... a portfolio of first-in-class WDR5 inhibitors for the ... WDR5 represent an exciting class of therapies, possessing ... for cancer patients. Substantial advances have been achieved ...
(Date:6/23/2016)... 2016  The Biodesign Challenge (BDC), a university competition ... harness living systems and biotechnology, announced its winning teams ... New York City . The ... projects at MoMA,s Celeste Bartos Theater during the daylong ... senior curator of architecture and design, and Suzanne ...
(Date:6/23/2016)... Apellis Pharmaceuticals, Inc. today announced positive ... its complement C3 inhibitor, APL-2. The trials were ... studies designed to assess the safety, tolerability, pharmacokinetics ... healthy adult volunteers. Forty subjects were ... dose (ranging from 45 to 1,440mg) or repeated ...
Breaking Biology Technology: