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Active [3H]-dopamine uptake by human lymphocytes: correlates with serotonin transporter activity
B A Faraj1, Z L Olkowski, R T Jackson
1Department of Radiology (Division of Nuclear Medicine), Emory University School of Medicine, Atlanta, Ga.
Human lymphocytes uptake [3H]-dopamine via a serotonin transporter, not dopamine transporters. This finding suggests lymphocytes may model neurological disorders affecting dopamine and serotonin uptake.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Dopamine and serotonin are crucial neurotransmitters involved in various neurological functions.
- Aberrant neurotransmitter uptake is implicated in psychiatric and addictive disorders.
- Lymphocytes offer a potential peripheral model for studying neurotransmitter transporter function.
Purpose of the Study:
- To investigate whether the uptake of [3H]-dopamine in human lymphocytes is mediated by a serotonin transporter.
- To characterize the affinity of selective serotonin and dopamine/norepinephrine transporter inhibitors for dopamine uptake in lymphocytes.
Main Methods:
- Assessed the effects of various monoamine uptake inhibitors on [3H]-dopamine uptake in human lymphocytes.
- Determined the 50% inhibiting concentration (IC50) for selective serotonin transporter inhibitors (indatraline, imipramine, fluoxetine).
- Determined the IC50 for selective dopamine and norepinephrine transporter inhibitors (bupropion, GBR 12909, nomifensine, xylamine).
Main Results:
- Selective serotonin transporter inhibitors potently inhibited [3H]-dopamine uptake in lymphocytes (IC50: 3.5-17 nmol/l).
- Selective dopamine/norepinephrine transporter inhibitors showed low affinity for lymphocyte dopamine uptake (IC50: 1,000-40,000 nmol/l).
- These results support the involvement of a serotonin transporter in lymphocyte dopamine uptake.
Conclusions:
- Human lymphocyte dopamine uptake is primarily mediated by a serotonin transporter.
- This high-affinity transport system in lymphocytes may serve as a valuable model for studying dopamine and serotonin uptake in neurological conditions.
- Lymphocyte-based models could aid in understanding and detecting changes associated with addictive and psychiatric disorders.
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