Characteristics of drug interactions with recombinant biogenic amine transporters expressed in the same cell type

Amy J. Eshleman, Marya Carmolli, Medhane Cumbay, Carey R. Martens, Kim A. Neve, Aaron Janowsky

Research output: Contribution to journalArticlepeer-review

198 Scopus citations


We characterized the effects of drugs on the uptake of [3H]neurotransmitter by and the binding of [125I](3β-(4- iodophenyl)tropane-2β-carboxylic acid methyl ester ([125I]RTI-55) to the recombinant human dopamine (hDAT), serotonin (hSERT), or norepinephrine (hNET) transporters stably expressed in human embryonic kidney 293 cells. RTI-55 had similar affinity for the hDAT and hSERT and lower affinity for hNET (K(d) = 1.83, 0.98, and 12.1 nM, respectively). Kinetic analysis of [125I]RTI-55 binding indicated that the dissociation rate (k-1) was significantly lower for hSERT and the association rate (k+1) was significantly lower for hNET compared with the hDAT. The potency of drugs at blocking [3H]neurotransmitter uptake was highly correlated with potency at blocking radioligand binding for hDAT and hSERT. Substrates were more potent at the inhibition of [3H]neurotransmitter uptake than radioligand binding. The potency of drugs was highly correlated between displacement of [3H]nisoxetine (K(d) = 6.0 nM) and [125I]RTI-55 from the hNET, suggesting that these radioligands recognize similar sites on the transporter protein. The correlation observed between inhibitory potency for uptake and binding of either ligand at the hNET was lower than correlations between uptake and binding for hDAT and hSERT. The present results indicate that the cocaine analog [125I]RTI-55 has unique binding properties at each of the transporters and that the use of recombinant transporters expressed by a single cell type can provide a powerful screening tool for drugs interacting with biogenic amine transporters, such as possible cocaine antagonists.

Original languageEnglish (US)
Pages (from-to)877-885
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
StatePublished - May 1999

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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