Studies of the biogenic amine transporters. 1. Dopamine reuptake blockers inhibit [3H]mazindol binding to the dopamine transporter by a competitive mechanism: Preliminary evidence for different binding domains

1994 ◽  
Vol 19 (2) ◽  
pp. 201-208 ◽  
Author(s):  
Christina M. Dersch ◽  
Hyacinth C. Akunne ◽  
John S. Partilla ◽  
George U. Char ◽  
Brian R. de Costa ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Biogenic Amine ◽  
Preliminary Evidence ◽  
Binding Domains ◽  
Mazindol Binding ◽  
Competitive Mechanism ◽  
Dopamine Reuptake ◽  
Biogenic Amine Transporters ◽  
Dopamine Reuptake Blockers

scholarly journals Studies of the Biogenic Amine Transporters 15. Identification of Novel Allosteric Dopamine Transporter Ligands with Nanomolar Potency

2015 ◽  
Vol 353 (3) ◽  
pp. 529-538 ◽  
Author(s):  
Richard B. Rothman ◽  
Subramaniam Ananthan ◽  
John S. Partilla ◽  
Surendra K. Saini ◽  
Omar Moukha-Chafiq ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Biogenic Amine ◽  
Biogenic Amine Transporters

Studies of the biogenic amine transporters. VIII: Identification of a novel partial inhibitor of dopamine uptake and dopamine transporter binding

Synapse ◽  
2002 ◽  
Vol 43 (4) ◽  
pp. 268-274 ◽  
Author(s):  
Richard B. Rothman ◽  
Christina M. Dersch ◽  
F. Ivy Carroll ◽  
Subramaniam Ananthan
Keyword(s):  
Dopamine Transporter ◽  
Biogenic Amine ◽  
Dopamine Uptake ◽  
Biogenic Amine Transporters

Studies of the biogenic amine transporters. 10. Characterization of a novel cocaine binding site in brain membranes prepared from dopamine transporter knockout mice

Synapse ◽  
2002 ◽  
Vol 44 (2) ◽  
pp. 94-105 ◽  
Author(s):  
Richard B. Rothman ◽  
F. Ivy Carroll ◽  
Marisela Morales ◽  
Daniel L. Rowley ◽  
Kenner C. Rice ◽  
...  
Keyword(s):  
Binding Site ◽  
Dopamine Transporter ◽  
Biogenic Amine ◽  
Knockout Mice ◽  
Brain Membranes ◽  
Biogenic Amine Transporters

scholarly journals Thermostabilization and purification of the human dopamine transporter (hDAT) in an inhibitor and allosteric ligand bound conformation

2018 ◽  
Author(s):  
Vikas Navratna ◽  
Dilip K. Tosh ◽  
Kenneth A. Jacobson ◽  
Eric Gouaux
Keyword(s):  
Dopamine Transporter ◽  
Limiting Factor ◽  
Molecular Architecture ◽  
Secondary Active Transport ◽  
Reward Seeking ◽  
Dopamine Reuptake ◽  
Seeking Behavior ◽  
Chemical Messenger ◽  
Hormonal Release ◽  
Detergent Micelles

AbstractThe human dopamine transporter(hDAT) plays a major role in dopamine homeostasis and regulation of neurotransmission by clearing dopamine from the extracellular space using secondary active transport. Dopamine is an essential monoamine chemical messenger that regulates reward seeking behavior, motor control, hormonal release, and emotional response in humans. Psychostimulants such as cocaine primarily target the central binding site of hDAT and lock the transporter in an outward-facing conformation, thereby inhibiting dopamine reuptake. The inhibition of dopamine reuptake leads to accumulation of dopamine in the synapse causing heightened signaling. In addition, hDAT is implicated in various neurological disorders and disease-associated neurodegeneration. Despite its significance, the molecular architecture of hDAT and its various conformational states are poorly understood. Instability of hDAT in detergent micelles has been a limiting factor in its successful biochemical, biophysical, and structural characterization. To overcome this hurdle, first we identified ligands that stabilize hDAT in detergent micelles. Then, we screened ∼200 single residue mutants of hDAT using high-throughput scintillation proximity assay, and identified a thermostable variant(I248Y). Here we report a robust strategy to overexpress and successfully purify a thermostable variant of hDAT in an inhibitor and allosteric ligand bound conformation.

Melatonin receptors limit dopamine reuptake by regulating dopamine transporter cell-surface exposure

2018 ◽  
Vol 75 (23) ◽  
pp. 4357-4370 ◽  
Author(s):  
Abla Benleulmi-Chaachoua ◽  
Alan Hegron ◽  
Marine Le Boulch ◽  
Angeliki Karamitri ◽  
Marta Wierzbicka ◽  
...  
Keyword(s):  
Cell Surface ◽  
Dopamine Transporter ◽  
Melatonin Receptors ◽  
Dopamine Reuptake

scholarly journals Cocaine and Antidepressant-Sensitive Biogenic Amine Transporters Exist in Regulated Complexes with Protein Phosphatase 2A

2000 ◽  
Vol 20 (20) ◽  
pp. 7571-7578 ◽  
Author(s):  
Andrea L. Bauman ◽  
Subbu Apparsundaram ◽  
Sammanda Ramamoorthy ◽  
Brian E. Wadzinski ◽  
Roxanne A. Vaughan ◽  
...  
Keyword(s):  
Biogenic Amine ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Phosphatase 2A ◽  
Biogenic Amine Transporters

scholarly journals Altered levels of dopamine transporter in the frontal pole and dorsal striatum in schizophrenia

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Hirotaka Sekiguchi ◽  
Geoff Pavey ◽  
Brian Dean
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Transporter ◽  
Molecular Mechanisms ◽  
Radioligand Binding ◽  
Dorsal Striatum ◽  
Synaptic Cleft ◽  
Human Brain Tissue ◽  
Frontal Pole ◽  
Postmortem Human Brain ◽  
Mazindol Binding

AbstractThe dopamine hypothesis proposes that there is a hypodopaminergic state in the prefrontal cortex and a hyperdopaminergic state in the striatum of patients with schizophrenia. Evidence suggests the hyperdopaminergic state in the striatum is due to synaptic dopamine elevation, particularly in the dorsal striatum. However, the molecular mechanisms causing disrupted dopaminergic function in schizophrenia remains unclear. We postulated that the dopamine transporter (DAT), which regulates intra-synaptic dopamine concentrations by transporting dopamine from the synaptic cleft into the pre-synaptic neuron, could be involved in dopaminergic dysfunction in schizophrenia. Therefore, we measured levels of DAT in the cortex and striatum from patients with schizophrenia and controls using postmortem human brain tissue. Levels of desmethylimipramine-insensitive mazindol-sensitive [3H]mazindol binding to DAT were measured using in situ radioligand binding and autoradiography in gray matter from Brodmann’s area (BA) 10, BA 17, the dorsal striatum, and nucleus accumbens from 15 patients with schizophrenia and 15 controls. Levels of desmethylimipramine-insensitive mazindol-sensitive [3H]mazindol binding were significantly higher in BA 10 from patients with schizophrenia (p = 0.004) and significantly lower in the dorsal striatum (dorsal putamen p = 0.005; dorsal caudate p = 0.007) from those with the disorder. There were no differences in levels of desmethylimipramine-insensitive [3H]mazindol binding in BA 17 or nucleus accumbens. These data raise the possibility that high levels of DAT in BA 10 could be contributing to lower synaptic cortical dopamine, whereas lower levels of DAT could be contributing to a hyperdopaminergic state in the dorsal striatum.

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