Researchers of the French CNRS have just revealed the structure of a receptor in mammals for the neurotransmitter serotonin – knowledge that could speed up the development of drugs very specific to this system and its related problems. Potential applications can already be imagined in chemotherapy, anesthesia and depression.
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In the middle of this International Year of Crystallography, the technique of honor has contributed to a discovery with the promise of significant drug-development applications for a diverse host of conditions: for the first time in a mammal, the structure of a serotonin receptor has been completely worked out. The research, carried out by scientists at France’s CNRS was published August 3rd in the journal Nature.
As a neurotransmitter, serotonin is responsible for transmitting signals between neurons. A message is received when the serotonin molecule attaches to a specific protein (a receptor) on the recipient cell’s surface. Understanding exactly how this receptor is built, its composition and organization, will help researchers understand how it operates in the serotonin messaging system. Until now, this family of receptors had only been studied in bacteria; the new work, in mice, provides an example that is structurally similar to the human receptor.
3D structure of the serotonin receptor (blue ribbons) inserted in a lipid membrane (black and red balls)
© Hugues Nury - Institut de biologie structurale (CNRS/CEA/Université Joseph Fourier)
The exciting result could be the creation of new medicines very precisely targeted at this system. The different conditions involved are numerous and varied, from the nausea associated with chemotherapy and anesthesia, to some types of depression, to digestive problems associated with the nervous system, like irritable bowel syndrome.
Without knowing the exact structure of the receptor targeted, the usual method of finding new drugs is to put many, many molecules to the test, in order to find one that has the desired effect. This new information, obtained after production of the mouse serotonin receptor protein in cell cultures in the lab, its purification, crystallization and, finally, x-ray analysis, should allow development of treatments tailored to fit this particular system, and much faster than before.