A Closer Look at Amphetamine-Induced Reverse Transport and Trafficking of the Dopamine and Norepinephrine Transporters |
| |
Authors: | S D Robertson H J G Matthies A Galli |
| |
Institution: | (1) Neuroscience Graduate Program, Vanderbilt University, Nashville, TN, USA;(2) Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA |
| |
Abstract: | Amphetamine (AMPH) and its derivatives are regularly used in the treatment of a wide array of disorders such as attention-deficit
hyperactivity disorder (ADHD), obesity, traumatic brain injury, and narcolepsy (Prog Neurobiol 75:406–433, 2005; J Am Med Assoc 105:2051–2054, 1935; J Am Acad Child Adolesc Psychiatry 41:514–521, 2002; Neuron 43:261–269, 2004; Annu Rev Pharmacol Toxicol 47:681–698, 2007; Drugs Aging 21:67–79, 2004). Despite the important medicinal role for AMPH, it is more widely known for its psychostimulant and addictive properties
as a drug of abuse. The primary molecular targets of AMPH are both the vesicular monoamine transporters (VMATs) and plasma
membrane monoamine—dopamine (DA), norepinephrine (NE), and serotonin (5-HT)—transporters. The rewarding and addicting properties
of AMPH rely on its ability to act as a substrate for these transporters and ultimately increase extracellular levels of monoamines.
AMPH achieves this elevation in extracellular levels of neurotransmitter by inducing synaptic vesicle depletion, which increases
intracellular monoamine levels, and also by promoting reverse transport (efflux) through plasma membrane monoamine transporters
(J Biol Chem 237:2311–2317, 1962; Med Exp Int J Exp Med 6:47–53, 1962; Neuron 19:1271–1283, 1997; J Physiol 144:314–336, 1958; J Neurosci 18:1979–1986, 1998; Science 237:1219–1223, 1987; J Neurosc 15:4102–4108, 1995). This review will focus on two important aspects of AMPH-induced regulation of the plasma membrane monoamine transporters—transporter
mediated monoamine efflux and transporter trafficking. |
| |
Keywords: | Amphetamine AMPH Norepinephrine transporter NET Dopamine transporter DAT Monoamine transporter Neurotransmitter transporter Monoamines Efflux Trafficking |
本文献已被 SpringerLink 等数据库收录! |
|