Localization and quantification of the dopamine transporter: comparison of [H]WIN 35,428 and [I]RTI-55 |
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Authors: | Cynthia L Coulter H Kevin Happe Debra A Bergman L Charles Murrin |
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Institution: | aDepartment of Neurology, Creighton University School of Medicine, 601 N. 30th Street, Omaha, NE 68131, USA bDepartment of Pharmacology, University of Nebraska Medical Center, 600 S. 42nd St., Omaha, NE 68198-6260, USA |
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Abstract: | Transport into the presynaptic terminal by the dopamine transporter is the primary mechanism for removing dopamine from the synaptic cleft. This transporter is a specific marker for dopamine terminals and is a primary site for CNS actions of cocaine. Several radioligands have been developed for analysis of the dopamine transporter. The ligands vary in affinity and specificity, leading to differences in reported transporter density in brain regions. We compared two of the most commonly used ligands, 3H]WIN 35,428 and 125I]RTI-55, analyzing the localization and density of sites in the rat brain using serial sections and quantitative autoradiography. Citalopram at 50 nmol/1 was used to block 125I]RTI-55 binding to serotonin transport sites. Transporter density was highest in the striatum and both ligands labeled equivalent numbers of sites, with lateral to medial and anterior to posterior gradients. In most areas the density of sites measured with the two ligands was similar. However, 125I]RTI-55 binding was significantly higher than 3H]WIN 35,428 binding in the substantia nigra zona compacta, ventral tegmental area, subthalamic nucleus and a number of other subcortical nuclear groups while 3H]WIN 35,428 binding was higher in lateral striatum and in olfactory tubercle. These differences could reflect different forms of the transporter, perhaps due to post-translational modifications, and they may provide a basis for differential pharmacological regulation of transporter function in discrete brain regions and disease states. |
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Keywords: | Dopamine transporter Cocaine receptor RTI-55 WIN 35 428 Quantitative autoradiography Dopamine metabolism Dopamine uptake |
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