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The present study elucidated the role of aspartate 345, a residue conserved in the third intracellular loop of all Na+/Cl(-)-dependent neurotransmitter transporters, in conformational changes of the dopamine (DA) transporter. Asparagine substitution (D345N) resulted in near normal transporter expression on the cell surface but caused extremely low Vmax and(More)
The effect of (+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT), a selective serotonin 5-HT1A agonist, on levels of extracellular norepinephrine (NE), dopamine (DA), and 5-HT (measured simultaneously) was investigated by microdialysis in the ventral tegmental area (VTA) of freely moving rats, and their behavioral activity was monitored. At 50(More)
Microdialysis was used to compare the effect of local perfusion of cocaine with that of functionally similar compounds on extracellular norepinephrine, dopamine, and serotonin (measured simultaneously) in the ventral tegmental area of freely moving rats. Tetrodotoxin (1 microM) potently inhibited both basal and cocaine-induced dialysate monoamine outputs.(More)
The present study addresses the effect of intracellular Na(+) and membrane potential on the binding of dopamine (DA) to the dopamine transporter (DAT). Perforation of plasma membranes of DAT-expressing cells with gramicidin diminished DA uptake and decreased the potency (increases K(i)) of DA in inhibiting the binding of cocaine analog(More)
The dopamine transporter mediates uptake of dopamine into neurons and is a major target for various pharmacologically active drugs and environmental toxins. Since its cloning, much information has been obtained regarding its structure and function. Binding domains for dopamine and various blocking drugs including cocaine are likely formed by interactions(More)
Extracellular levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were measured simultaneously by microdialysis in the ventral tegmental area (VTA) of conscious rats, and locomotor activity was monitored. Extracellular NE, DA and 5-HT was increased by both local infusion (30 microM) and i.p. injection (20 and 40 mg/kg) of cocaine with 5-HT(More)
PURPOSE Assessment of the absorption, metabolism and excretion of [(14)C]-lenalidomide in healthy male subjects following a single oral dose. METHODS Six healthy male subjects were administered a single 25 mg oral suspension dose of [(14)C]-lenalidomide. Blood (plasma), semen and excreta were collected. Mass balance assessments were done by radioactivity(More)
The present study examines the interaction of Na+ and K+ with the binding of the cocaine analogue 3beta-(4-[125I]iodophenyl)tropane-2beta-carboxylic acid isopropyl ester to dopamine transporters (DATs) in rat striatal synaptosomal membranes at 37 degrees C. The binding increases with [Na+] from 10 to 100 mM and decreases with higher [Na+]. The presence of(More)
The effect of covalent sulfhydryl modification on dopamine uptake by the human dopamine transporter was determined by rotating disc electrode voltammetry. A transporter construct, X5C, with five mutated cysteines (C90A, C135A, C306A, C319F, and C342A) and the constructs into which the wild-type cysteines were substituted back into X5C, one at a time, all(More)
The present study describes the binding of cocaine analog [125I]3 beta-(iodophenyl)tropan-2 beta-carboxylic acid isopropyl ester ([125I]RTI-121), a highly selective ligand for the dopamine transporter (DAT), to rat striatal synaptosomal membranes at 37 degrees C. Saturation analysis of [125I]RTI-121 binding revealed a single binding site with similar(More)