Multiple Binding Sites for [125I]RTI-121 and Other Cocaine Analogs in Rat Frontal Cerebral Cortex
Document Type
Article
Publication Date
9-1-1998
Description
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 [125I]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 [125I]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: [125I] 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- 121 and the presence of several known transporters in the tissue studied.
Citation Information
Boja, J. W.; Carroll, F. I.; Vaughan, R. A.; Kopajtic, T.; and Kuhar, M. J.. 1998. Multiple Binding Sites for [125I]RTI-121 and Other Cocaine Analogs in Rat Frontal Cerebral Cortex. Synapse. Vol.30(1). 9-17. https://doi.org/10.1002/(SICI)1098-2396(199809)30:1<9::AID-SYN2>3.0.CO;2-7 PMID: 9704876 ISSN: 0887-4476