Viable dopamine neurons in Parkinson's disease express the dopamine transporter (DAT) and release dopamine (DA). We postulated that potent DAT inhibitors, with low affinity for the serotonin transporter (SERT), may elevate endogenously released extracellular dopamine levels to provide therapeutic benefit. The therapeutic potential of eight DAT inhibitors was investigated in 1-methyl-4-phenyl-1,...

Synaptic re-uptake of dopamine is dependent on the dopamine transporter (DAT), which is regulated by its distribution to the cell surface. DAT trafficking is modulated by the Parkinson's disease-linked protein alpha-synuclein, but the contribution of synuclein family members beta-synuclein and gamma-synuclein to DAT trafficking is not known. Here we use SH-SY5Y cells as a model of DAT trafficki...

The neuronal dopamine transporter (DAT) is a major determinant of extracellular dopamine (DA) levels and is the primary target for a variety of addictive and therapeutic psychoactive drugs. DAT is acutely regulated by protein kinase C (PKC) activation and amphetamine exposure, both of which modulate DAT surface expression by endocytic trafficking. In order to use live imaging approaches to stud...

OBJECTIVE The direct antiglobulin test (DAT) is an important tool for identification of haemolytic disease of the newborn (HDN) caused by erythrocyte immunization. Although this test has been used for decades, accurate insights into its diagnostic properties and optimal use in the diagnosis of HDN are limited. We aimed to gain more insight into the diagnostic properties of the DAT for HDN by co...

The neuronal dopamine transporter (DAT) plays a key role in terminating dopaminergic chemical neurotransmission; thus, the study of the regulation of DAT activity is important in defining parameters relevant to the control of dopaminergic neurotransmission. Interpretation of the results from previous work of this laboratory suggests that occupation of presynaptic autoreceptors increases DAT act...

Dynamic membrane trafficking of the monoamine dopamine transporter (DAT) regulates dopaminergic signaling. Various intrinsic and pharmacological modulators can alter this trafficking. Previously we have shown ethanol potentiates in vitro DAT function and increases surface expression. However, the mechanism underlying these changes is unclear. In the present study, we found ethanol directly regu...

Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the distal C terminus of DAT and colocalized with DAT in dopaminergic neurons. CaMKIIalpha stimulated dop...

A new direct agglutination test (DAT) for use with urine samples for the diagnosis of visceral leishmaniasis (VL) has been developed and compared with the conventional DAT with serum samples and our previously reported enzyme-linked immunosorbent assay (ELISA) with urine samples (urine ELISA). The new DAT, in which anti-human IgG was used as enhancing antibody, was tested with urine samples fro...

Dopaminergic signaling and plasticity are essential to numerous CNS functions and pathologies, including movement, cognition, and addiction. The amphetamine- and cocaine-sensitive dopamine (DA) transporter (DAT) tightly controls extracellular DA concentrations and half-life. DAT function and surface expression are not static but are dynamically modulated by membrane trafficking. We recently dem...