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High‐affinity binding of [ 125 I]RTI‐55 to dopamine and serotonin transporters in rat brain
Author(s) -
Boja J. W.,
Mitchell W. M.,
Patel A.,
Kopajtic T. A.,
Carroll F. I.,
Lewin A. H.,
Abraham P.,
Kuhar M. J.
Publication year - 1992
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890120104
Subject(s) - dopamine transporter , dopamine , striatum , serotonin , dopaminergic , chemistry , dopamine plasma membrane transport proteins , ligand (biochemistry) , serotonergic , serotonin transporter , 5 ht receptor , binding site , biochemistry , pharmacology , receptor , medicine , endocrinology , biology
RTI‐55 (3β‐(4‐iodophenyl)tropan‐2β‐carboxylic acid methyl ester), one of the most potent inhibitors of dopamine uptake reported to date, was radioiodinated and tested as a probe for the cocaine receptor in Sprague‐Dawley rat brain. Saturation and kinetic studies in the striatum revealed that [ 125 I]RTI‐55 bound to both a high‐ and low‐affinity site. The K d for the high‐affinity site was 0.2 nM, while the K d for the low‐affinity site was 5.8 nM. The corresponding number of binding sites in the striatum was 37 and 415 pmol/g protein. The pharmacological profile of specific [ 125 I]RTI‐55 binding in the striatum was consistent with that of the dopamine transporter. Additionally, [ 125 I]RTI‐55 was found to bind with high affinity to the cerebral cortex. Scatchard analysis revealed a single high‐affinity component of 0.2 nM with a density of 2.5 pmol/g protein. The pharmacological profile demonstrated by [ 125 I]RTI‐55 in the cerebral cortex matched that of the serotonin transporter. Autoradiographic analysis of sagittal brain sections with [ 125 I]RTI‐55 binding was consistent with these findings. Specific binding of [ 125 I]RTI‐55 was blocked by dopamine uptake inhibitors in areas rich in dopaminergic nerve terminals. Conversely, serotonin uptake inhibitors blocked the binding of [ 125 I]RTI‐55 in brain areas rich in serotonergic neurons. These results demonstrate that [ 125 I]RTI‐55 may be a very useful ligand for the dopamine and serotonin transporters. Published 1992 Wiley‐Liss, Inc.