Researchers have long known that the wily marine snail known as conus geographus uses a toxic venom to stun its prey into submission.

Now, researchers led by a UC San Francisco scientist have determined that proteins extracted from the venom prevent serotonin, a key chemical messenger in the nervous system, from acting at a particular molecular gateway, or receptor, in African toad eggs. The receptor is also found in the human brain.

The finding, reported in the current issue of Science, could provide a model for exploring the way in which serotonin and several other neurotransmitter receptors are regulated in humans, according to one of the authors of the study,

David Julius, PhD, an associate professor of cellular and molecular pharmacology at UCSF. And as serotonin plays a key role in regulating nerve cell behavior, understanding the way in which it functions paves the way for designing new drugs to control its actions.

One existing drug that targets the receptor, known as 5-HT3, is used to treat nausea that accompanies chemotherapy. Drugs targeting the receptor could potentially be designed to treat pain and anxiety, said Julius.

Serotonin and the hundreds of other neurotransmitters zipping through the brain act as chemical messengers between nerve cells. They are released from one neuron and move at the rate of milliseconds to another, where they bind to a particular molecular gateway within the cell. There, like a key turned in a keyhole, they "unlock" the gateway, transmitting their chemical message into the cell, telling it either to fire an electrical output, or nerve signal, or hold off on firing.

The ultimate goal of the current study, said lead author Laura England, PhD, a postdoctoral candidate in Julius's lab, is to use the toxins that have been isolated to probe the site at which serotonin binds to the receptor and understand what the molecular pocket at which it binds looks like.

"If you can do that, and figure out what
'"/>

Contact: Jennifer O'Brien
jobrien@itsa.ucsf.edu
415-476-2557
University of California - San Francisco
24-Jul-1998