Regulation of the functional activity of the human dopamine transporter by the arachidonic acid pathway

European Journal of Pharmacology
L Zhang, M E Reith

Abstract

The role of arachidonic acid was examined in the regulation of dopamine transport in C6 glioma cells stably expressing the human dopamine transporter. Exogenously added arachidonic acid (20-160 microM) stimulated [3H]dopamine uptake when pre-incubated for short times (15-30 min); 160 microM arachidonic acid inhibited following longer pre-exposures (45-60 min). Under the same conditions, only decreases were observed in the binding of the cocaine analog [3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane ([3H]WIN 35,428). The reduction in dopamine transporter activity by arachidonic acid (at 160 microM for 60 min) was caused by a decrease in the Vmax (from 202 to 44 pmol/mg/min) opposed by a smaller reduction in K(m) (from 1.2 to 0.8 microM), whereas the effect of arachidonic acid (at 160 microM for 15 min) on [3H]WIN 35,428 binding was caused by a reduction in the Bmax (from 1.8 to 1.3 pmol/mg) without a change in Kd (7.2 nM). Upon 15-min exposure, melittin, an activator of phospholipase A2, and nordihydroguaiaretic acid, a lipooxygenase inhibitor, both expected to cause enhanced endogenous arachidonic acid, inhibited [3H]dopamine uptake and [3H]WIN 35,428 binding with an IC50 value close to 1 microM, whereas thimerosal, whic...Continue Reading

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Citations

Oct 25, 2003·European Journal of Pharmacology·Nianhang ChenMaarten E A Reith
Nov 13, 2003·European Journal of Pharmacology·Ole V Mortensen, Susan G Amara
Aug 26, 1998·Biochimica Et Biophysica Acta·N V RalstonH H Schmid
Sep 11, 2002·European Journal of Pharmacology·Brian M RossSylvie D Turenne
Apr 11, 1997·European Journal of Pharmacology·M E ReithN H Chen
Dec 29, 1998·European Journal of Pharmacology·J M KokoshkaA E Fleckenstein
Sep 23, 2003·Psychiatry Research·Laure Buydens-BrancheyJoseph R Hibbeln
Dec 13, 2001·Neurochemistry International·Warren SuChung-Ren Jan
Oct 16, 2009·Molecular Interventions·Christopher B Divito, Susan G Amara
Nov 5, 2002·Annual Review of Pharmacology and Toxicology·Richard Nass, Randy D Blakely
Jun 14, 2005·Biological Psychiatry·Bertha K MadrasAlan J Fischman
Feb 1, 2003·Journal of Neurochemistry·Rhonda Jo PearlmanRobert J Vandenberg
Mar 6, 2010·Annals of the New York Academy of Sciences·Kyle C Schmitt, Maarten E A Reith
Sep 24, 2008·Handbook of Clinical Neurology·Richard B Mailman, Xuemei Huang
May 11, 2006·Molecular Pharmacology·Kristopher M KahligAurelio Galli
Nov 4, 2004·Journal of Receptor and Signal Transduction Research·Kim A NeveHeather Trantham-Davidson
Jul 30, 2002·Prostaglandins, Leukotrienes, and Essential Fatty Acids·B M Ross, S D Turenne

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