Boja J W, Cadet J L, Kopajtic T A, Lever J, Seltzman H H, Wyrick C D, Lewin A H, Abraham P, Carroll F I
Molecular Pharmacology Section, National Institutes of Health/National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland 21224, USA.
Mol Pharmacol. 1995 Apr;47(4):779-86.
The iodine-125 analog of the dopaminergically selective cocaine analog 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester (RT1-121) was evaluated as a probe for the dopamine transporter in rat striatum. Saturation and kinetic studies indicated that [125I]RTI-121 binds to both high and low affinity components. The Kd of the high affinity component was 0.14 +/- 0.01 nM (mean +/- standard error), whereas the low affinity component demonstrated an affinity of 1.59 +/- 0.09 nM. The corresponding numbers of striatal binding sites labeled by [125I]RTI-121 were 295 +/- 6 and 472 +/- 59 pmol/g of tissue (original wet weight), respectively. Intrastriatal injections of 6-hydroxydopamine eliminated > 90% of specific [125I]RTI-121 binding in the striatum. The pharmacological profile of specific [125I]RTI-121 binding in the rat striatum was consistent with that of the dopamine transporter. There was a strong (r = 0.98, p < 0.0001) correlation between the potencies of drugs that displaced specific [125I]RTI-121 binding and the potencies of these drugs to inhibit the uptake of [3H]dopamine. In contrast, no correlation was found for the potencies of drugs to inhibit the uptake of either [3H]norepinephrine or [3H]serotonin. Autoradiographs produced using [125I]RTI-121 demonstrated a distribution of label consistent with the distribution of dopaminergic neurons in rat brain. Because of its high affinity and high selectivity for the dopamine transporter, [125I]RTI-121 may be an extremely useful ligand for the dopamine transporter.
多巴胺能选择性可卡因类似物3β-(4-碘苯基)托烷-2β-羧酸异丙酯（RTI-121）的碘-125类似物被评估为大鼠纹状体中多巴胺转运体的一种探针。饱和与动力学研究表明，[125I]RTI-121与高亲和力和低亲和力成分均有结合。高亲和力成分的解离常数（Kd）为0.14±0.01 nM（平均值±标准误差），而低亲和力成分的亲和力为1.59±0.09 nM。[125I]RTI-121标记的纹状体结合位点数量分别为295±6和472±59 pmol/g组织（原始湿重）。纹状体内注射6-羟基多巴胺消除了纹状体中>90%的特异性[125I]RTI-121结合。大鼠纹状体中特异性[125I]RTI-121结合的药理学特征与多巴胺转运体的特征一致。在取代特异性[125I]RTI-121结合的药物效力与这些药物抑制[3H]多巴胺摄取的效力之间存在强相关性（r = 0.98，p < 0.0001）。相比之下，未发现药物抑制[3H]去甲肾上腺素或[3H]5-羟色胺摄取的效力之间存在相关性。使用[125I]RTI-121产生的放射自显影片显示标记分布与大鼠脑中多巴胺能神经元的分布一致。由于其对多巴胺转运体具有高亲和力和高选择性，[125I]RTI-121可能是一种对多巴胺转运体极其有用的配体。
