An interdisciplinary team of researchers from the University of Texas Medical Branch at Galveston and the University of Houston has found a new way to influence the vital serotonin signaling system — possibly leading to more effective medications with fewer side effects.
Scientists have linked malfunctions in serotonin signaling to a wide range of health issues, everything from depression and addictions to epilepsy and obesity and eating disorders. Much of their attention has focused on complex proteins called serotonin receptors, which are located in the cell membrane. Each receptor has a so-called “active site” specially suited to bond with a serotonin molecule; when that bond is formed, the receptor changes shape, transmitting a signal to the cell’s interior.
Traditional drug discovery efforts target interactions that take place at such active sites. But a receptor’s behavior can also be changed by additional proteins that bind to the receptor at locations quite distant (in molecular terms) from the active site, in a process called “allosteric regulation” — the mechanism examined by the UTMB-UH team for one specific and highly significant kind of serotonin receptor, designated the 5-HT2C.
“This is a whole new way of thinking about this system, targeting these interactions,” said UTMB professor Kathryn Cunningham, senior author of a paper on the research now online in the Journal of Neuroscience. “Basically, we’ve created a new series of molecules and validated that we can use them to change the way the receptor functions both in vitro and in vivo, through an allosteric effect.”