Active [³H]-Dopamine Uptake by Human Lymphocytes: Correlates with Serotonin Transporter Activity

Abstract

The main objective of the present investigation was to determine whether the uptake of [³H]-dopamine in human lymphocytes is mediated through a serotonin transporter. This was examined by studying the effects of various monoamine uptake inhibitors on the uptake of [³H]-dopamine in human lymphocytes. Among the compounds tested, indatraline, imipramine and fluoxetine, selective inhibitors of neuronal serotonin transporter, were the most potent inhibitors of [³H]-dopamine uptake in lymphocytes. The 50% inhibiting concentration (IC50) for these inhibitors was in the range of 3.5-17 nmol/l. Bupropion, GBR 12909, nomifensine and xylamine, selective inhibitors of dopamine and norepinephrine transporters, had low affinity for the dopamine uptake system in human lymphocytes with IC50 values ranging between 1,000 and 40,000 nmol/l. These findings provide supportive evidence for the participation of a serotonin transporter in the uptake of [³H]-dopamine in human lymphocytes. The existence of a high affinity transport system for dopamine and serotonin in human lymphocytes may serve as a readily accessible model to detect changes in the neuronal uptake of dopamine and serotonin in addictive and psychiatric disorders.

Thioether Metabolites of 3,4-Methylenedioxyamphetamine and 3,4-Methylenedioxymethamphetamine Inhibit Human Serotonin Transporter (hSERT) Function and Simultaneously Stimulate Dopamine Uptake into hSERT-Expressing SK-N-MC Cells

“…10), indicating that DA entered the cell via the hSERT. Indeed, functional SERT proteins are capable of transporting DA into 5-HT cells (Schmidt and Lovenberg, 1985;Faraj et al, 1994). Although the mechanism by which MDMA/MDA and the metabolites stimulate DA uptake by the hSERT is not known, Saldana and Barker (2004) have recently reported that elevated temperature alters SERT-mediated 5-HT and DA transport, such that the relative selectivity of the SERT for DA increases significantly at the higher temperature.…”

“…MDMA-induced serotonergic neurotoxicity also seems to be coupled to increases in dopamine (DA) release (Bankson and Cunningham, 2001). MDMA stimulates the release of DA (Gudelsky and Nash, 1996;Koch and Galloway, 1997), and functional SERTs are capable of transporting DA into 5-HT cells (Schmidt and Lovenberg 1985;Faraj et al, 1994). The subsequent monoamine oxidase (MAO)-B-mediated oxidation of DA within the 5-HT nerve terminal may contribute to MDMA-induced generation of reactive oxygen species (ROS; Sprague and Nichols, 1995;Sprague et al, 1998).…”

Regional Differences in Extracellular Dopamine and Serotonin Assessed by In Vivo Microdialysis in Mice Lacking Dopamine and/or Serotonin Transporters

“…Some of these adaptive changes could come from involvement of redundant monoaminergic systems in cocaine reward. Since each transporter displays significant affinities for each monoamine (Faraj et al, 1994;Giros et al, 1994;Gu et al, 1994;Eshleman et al, 1999), the absence of its cognate transporter might allow a monoamine to diffuse further from its site of release and be accumulated by another transporter.…”

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) Is Incorporated into Rat Splenocytes, Thymocytes, and Hepatocytes Through Monoamine Transporters and Induces Apoptosis

“…It was reported that the inhibitory eŠects of indatraline on uptake of [ 3 H]-DA into human lymphocytes were stronger than those of nomifensine. 8) Although nomifensine is known as an inhibitor of DA-transporter, it also bind to norepinephrine transporter with high a‹nity. 19) Thus, the uptake of Trp-P-1 may be mediated not only by DA and 5-HT transporters but also by the norepinephrine transporter, suggesting that monoamine transporters play as important roles in the uptake of Trp-P-1.…”

“…6) In addition, the transport systems of DA and 5-HT exist not only in synapses but also in platelets and lymphocytes. 7,8) Trp-P-1 was detectable in platelets for at least 9 days after oral administration to rabbits. 9) In this study, we investigated how Trp-P-1 is incorporated into splenocytes, thymocytes, and hepatocytes, and stimulates the apoptotic pathway.…”