The vesicular monoamine transporter is not regulated by dopaminergic drug treatments.
The number of neuronal synaptic vesicular monoamine transporters (vesicular monoamine transporter type 2; VMAT2) has been recently proposed as an index of monoamine presynaptic terminal density. The present study investigated the possible regulation of the vesicular monoamine transporter. Rats were treated for 2 weeks with drugs known to influence dopaminergic neurotransmission, including those commonly used in the treatment of Parkinson's disease. Autoradiographic assays were performed using [3H]methoxytetrabenazine, [3H]raclopride, and [3H]WIN 35,428 ([3H]2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) to measure vesicular monoamine transporter, dopamine D2 receptor and synaptic plasma membrane dopamine re-uptake site bindings, respectively. None of the drug treatments significantly modified levels of vesicular monoamine transporter binding. In contrast, both dopamine D2 receptors and dopamine re-uptake sites were altered by some of the treatment regimens. These data extend preliminary results that suggest the vesicular monoamine transporter is not easily regulated and confirm the plasticity of dopamine D2 receptors and the dopamine re-uptake site. Measures of striatal vesicular monoamine transporter density may, thus, provide objective estimates of monoaminergic innervation in neurodegenerative diseases, unaffected by the use of symptomatic therapies.
Vander Borght
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T
Department of Internal Medicine (Division of Nuclear Medicine), The University of Michigan, Ann Arbor, USA.
Kilbourn
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M
Desmond
T
T
Kuhl
D
D
Frey
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K
D000818:Animals; D001692:Biological Transport; D004298:Dopamine / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000502:physiology; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology; D013569:Synapses / Q000502:physiology; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D017448:Receptors, Dopamine D2; C493454:Slc18a2 protein, rat; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C084867:5-O-methyldihydrotetrabenazine; D004298:Dopamine; D013747:Tetrabenazine