Inhibition by arachidonic acid and other fatty acids of dopamine uptake at the human dopamine transporter
| Autor: | Maarten E.A. Reith, Janet L. Berfield, Michael Appell, Nianhang Chen |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Cell Survival
Polyunsaturated Alkamides Dopamine Linoleic acid Carboxylic Acids Dopamine transport Nerve Tissue Proteins Arachidonic Acids Kidney Second Messenger Systems Dopamine agonist Cell Line Membrane Lipids Structure-Activity Relationship chemistry.chemical_compound Membrane Transport Modulators medicine Humans Electrodes Pharmacology chemistry.chemical_classification Dopamine Plasma Membrane Transport Proteins Arachidonic Acid Membrane Glycoproteins Cell Membrane Fatty Acids Membrane Transport Proteins Fatty acid Anandamide Calcium Channel Blockers Hydrocarbons Kinetics Oleic acid chemistry Biochemistry Eicosanoids Arachidonic acid Stearic acid Endocannabinoids medicine.drug |
| Zdroj: | European Journal of Pharmacology. 478:89-95 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2003.08.045 |
| Popis: | It is known that arachidonic acid, in addition to promoting release of dopamine, can inhibit its transport. The present study provides preliminary information on structure-activity relationships for uptake inhibition by rotating disk voltammetry in human embryonic kidney-293 cells expressing the human dopamine transporter. Except for anandamide, all other fatty acids studied at a pretreatment concentration of 80 microM caused significant reductions in Vmax but not Km. Increasing saturation of the hydrocarbon tails (partial saturation: oleic acid, linoleic acid; full saturation: arachidic acid, stearic acid, stearic acid ethyl ester) removed inhibitory activity incrementally, suggesting a role for cis-unsaturation (folding/bending of hydrocarbon tails). The relative lack of effect of 5,8,11,14-eicosatetraynoic acid also supports the idea that less linear structures are less inhibitory on dopamine uptake. Esterification of the free carboxylic group (arachidonic acid ethyl ester) prevented most of the inhibitory activity, arguing against mere membrane lipid disruption. Finally, the endogenous cannabinoid anandamide greatly reduced uptake Vmax accompanied by a small decrease in Km, a potentially important effect on dopaminergic neurotransmission. |
| Databáze: | OpenAIRE |
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