Multiple binding sites for I-125 RTI-121 and other cocaine analogs in rat frontal cerebral cortex

Multiple binding sites for I-125 RTI-121 and other cocaine analogs in rat frontal cerebral cortex

Boja J W; Carroll F I; Vaughan R A; Kopajtic T; Kuhar M J

Synapse

1998

1998-09

In an effort to identify novel binding sites for cocaine and its analogs, we carried out binding studies with the high-affinity and selective ligand [I-125]RTI-121 in rat frontal cortical tissue. Very low densities of binding sites were found. Saturation analysis revealed that the binding was to both high- and low-affinity sites. Pharmacological competition studies were carried out with inhibitors of the dopamine, norepinephrine, and serotonin transporters. The various transporter inhibitors inhibited the binding of 15 pM [I-125]RTI-121 in a biphasic fashion following a two-site binding model. The resultant data were complex and did not suggest a simple association with any single transporter. Correlational analysis supported the following hypothesis: [I-125] RTI-121 binds to known transporters and not to novel sites; these include dopamine, norepinephrine, and serotonin transporters. Immunoprecipitation of transporters photoaffinity labeled with [(125)] RTI-82 and subsequent analysis of SDS-page gels revealed the presence of authentic dopamine transporters in these samples; displacement of the photoaffinity label occurred with a typical dopamine transporter pharmacology. These data are compatible with the binding properties of RTI-181 and the presence of several known transporters in the tissue studied. Synapse 30:9-17, 1998. (C) 1998 Wiley-Liss, Inc.dagger

Neurosciences & Neurology; localization; h-3 gbr-12935 binding; transporter; membranes; dopamine transporter; cocaine; nucleus-accumbens; norepinephrine transporter; medial prefrontal cortex; brain synaptosomes; glycosylation; human dopamine; reinforcing properties; RTI-121; self-stimulation; serotonin transporter; striatal

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