Signaling

Randy Blakely, Ph.D.

Professor of Pharmacology

Suite 7140 MRBIII Vanderbilt University School of Medicine, Nashville, TN, 37232-8548
(615) 936-3705 (office)

Research Description

Once released into the synaptic cleft, neurotransmitters like serotonin (5HT) and norepinephrine (NE) must be quickly removed to limit the magnitude and duration of chemical signaling. The principal mechanism for 5HT and NE clearance is active transport back into neuronal terminals. Drugs with important clinical or addictive properties, including antidepressants, cocaine and amphetamines, block the access of 5HT and NE to transport sites and thus prolong their action. Using chimera studies and site-directed mutagenesis, we are exploring structural domains that lead to neurotransmitter and antagonist specificity for 5HT and NE transporters. With site specific antibodies and electrophysiologic techniques, we are evaluating post-translational mechanisms involved in acute carrier regulation in vitro and in vivo. Finally, we are exploring the effects of targeted transporter mutations using transgenic mice as a model for the behavioral and neurologic consequences of transporter defects in humans.

Selected Publications