Premium
Ethanol potentiates the function of the human dopamine transporter expressed in Xenopus oocytes
Author(s) -
Mayfield R. Dayne,
Maiya Rajani,
Keller Denise,
Zahniser Nancy R.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00656.x
Subject(s) - xenopus , dopamine transporter , dopamine , chemistry , ethanol , microbiology and biotechnology , transporter , neuroscience , function (biology) , dopamine plasma membrane transport proteins , medicine , endocrinology , biology , biochemistry , gene , dopaminergic
Ethanol alters a variety of properties of brain dopaminergic neurons including firing rate, synthesis, release, and metabolism. Recent studies suggest that ethanol's action on central dopamine systems may also involve modulation of dopamine transporter (DAT) activity. The human DAT was expressed in Xenopus oocytes to examine directly the effects of ethanol on transporter function. [ 3 H]Dopamine (100 n m ) accumulation into DAT‐expressing oocytes increased significantly in response to ethanol (10 min; 10–100 m m ). In two‐electrode voltage‐clamp experiments, DAT‐mediated currents were also enhanced significantly by ethanol (10–100 m m ). The magnitude of the ethanol‐induced potentiation of DAT function depended on ethanol exposure time and substrate concentration. Cell surface DAT binding ([ 3 H]WIN 35,428; 4 n m ) also increased as a function of ethanol exposure time. Thus, the increase in dopamine uptake was associated with a parallel increase in the number of DAT molecules expressed at the cell surface. These experiments demonstrate that DAT‐mediated substrate translocation and substrate‐associated ionic conductances are sensitive to intoxicating concentrations of ethanol and suggest that DAT may represent an important site of action for ethanol's effects on central dopaminergic transmission. A potential mechanism by which ethanol acts to enhance DAT function may involve regulation of DAT expression on the cell surface.