Scientists uncover molecular changes underlying amphetamine and antidepress...( Although our neurons make a mess when...)

Although our neurons make a mess when they talk to each other, they come equipped with their own maid service of sorts. Nerve endings are studded with proteins called transporters that act as molecular vacuum cleaners, clearing the synapse of released chemical messengers.

Transporters are critical to normal communication in the brain, and they are targets for both therapeutic drugs and drugs of abuse. The transporter for the neurotransmitter serotonin, for example, is blocked by antidepressants like Prozac and is a site of action for cocaine and amphetamines.

Vanderbilt University Medical Center scientists studying the serotonin transporter have discovered novel regulatory mechanisms that move the transporter on and off the cell surface. They report their findings, which point to new actions for antidepressants and psychostimulants, in the July 30th issue of Science.

"We thought for a long time that transporters sat there and basically drained away neurotransmitter," said Randy D. Blakely, Ph.D., Allan D. Bass Professor of Pharmacology and director of the Center for Molecular Neuroscience. "We've learned that these machines are much more complicated than we once thought."

Earlier studies had demonstrated that the transporter could be chemically modified in response to activated signaling pathways inside the neuron. The modification -- an addition of phosphate groups called phosphorylation -- of the transporter is linked to its disappearance from the cell surface.

"But the problem is, you could have a situation where other signals pull the transporter off the cell surface right when it needs to be there to clear away serotonin," Blakely said. "In this case, the signals coming into the neuron would have more priority than the neurotransmitter itself."

He and Sammanda Ramamoorthy, Ph.D., research assistant professor of Pharmacology, wondered whether there was a way for the transporter to 'ignore' these inside signals when it needed to
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Contact: Matt Scanlan
matt.scanlan@mcmail.vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
30-Jul-1999