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Inhibition by arachidonic acid and other fatty acids of dopamine uptake at the human dopamine transporter
Nianhang Chen1, Michael Appell2, Janet L. Berfield2 and Maarten E. A. Reith, , 1
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Box 1649, Peoria, IL 61656-1649, USA
Received 12 May 2003; revised 19 August 2003; accepted 25 August 2003. ; Available online 30 September 2003.
Abstract
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 μM 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.I always eat an egg in the morning.But you know what i didn’t know the reason that why all prefers to eat in the morning.I have gone through your post and i really got a useful information on why it is necessary to eat eggs in the morning.
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