One new method may be able to lead to more efficient medications, with fewer negative effects, according to research published within the Journal of Neuroscience.

Scientists from the University of Texas Medical Branch (UTMB) at Galveston and also the University of Houston found a new way to help the vital serotonin signaling system. The team linked malfunctions in serotonin signaling to a selection of health issues, including from depression and addictions, to epilepsy and obesity.

Much of the attention centered on complex proteins referred to as serotonin receptors, that are found in the cell membrane. All these receptors have “active sites” suitable for bond having a serotonin molecule.

Traditional drug discovery efforts target interactions that take place at these sites, but a receptor’s behavior could be changed by additional proteins that bind into it at locations farther from the active site. This process is called “allosteric regulation.”

“This can be a totally new way of thinking relating to this system, targeting these interactions,” said UTMB professor Kathryn Cunningham, senior author of a paper on the research. “Basically, we’ve created a new series of molecules and validated that people can use these to change the way the receptor functions in vitro and in vivo, with an allosteric effect.”

The group centered on the natural interaction between the 5-HT2C receptor, serotonin, and a molecule called PTEN, which controls 5-HT2C receptor function. I was told that that it’s possible for a receptor to bind to serotonin, and PTEN simultaneously, which causes an allosteric effect where serotonin is diminished.

“We want to maintain signaling through 5-HT2C receptors to gain therapeutic benefits, and to do this we had to lessen the number of receptors that were binding to PTEN molecules,” said UH professor Scott Gilbertson, another senior author on the paper. “One way to do that is to develop an inhibitor that competes with the receptor for binding to PTEN.”

The researchers chose a fragment from the part of the receptor where PTEN attached. These sub-protein structures are classified as “peptides.” The team also checked out behavioral studies in laboratory rats, which established that 3L4F increased 5-HT2C responses.

“We looked at both human cells and rats because ultimately we want to translate these studies into therapeutics,” said UTMB postdoctoral fellow Noelle Anastasio, lead author from the paper. “The thought of targeting these interactions to produce drug and research tools is really new and has great potential.”

With this research, they determined that elements of peptides were important to bonding with PTEN. These details can be used to design smaller molecules with the same or better activity.

“We’ve got the fundamentals down now, therefore we may use the chemistry to make new molecules that we think may be potentially helpful for management of addictions, for example,” Cunningham said. “But there’s also a powerful interest in determining the biology of this interaction between 5-HT2C and PTEN, what it really means when it comes to disease states such as the addictions, alcoholism, depression and obesity and eating disorders. I think in a broader sense this is actually likely to allow us to understand the neurobiology of those disorders.”

Recently, researchers published another study within the Journal of Neuroscience about how exactly tracking just one protein that regulates serotonin assists you to study the dynamics from the protein that regulates mood, appetite and sleep. The team within this research needed to tag these proteins to be able to follow their motion at first glance of cells instantly.

“By understanding the basic mechanisms that naturally turn serotonin transporter activity up and down, maybe we can develop medications that leave milder side-effects and also have even greater efficacy,” said Randy Blakely, the Allan D. Bass Professor of Pharmacology and Psychiatry. “Our sights will also be focused on transferring what we should have learned with normal serotonin transporters for an knowledge of the hyperactive transporters recommendations in youngsters with autism.”