Dopamine neuronal transport kinetics and effects of amphetamine

被引:101
作者
Jones, SR
Joseph, JD
Barak, LS
Caron, MG
Wightman, RM
机构
[1] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Curriculum Neurobiol, Chapel Hill, NC 27599 USA
[3] Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Cell Biol, Durham, NC 27710 USA
[4] Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Med, Durham, NC 27710 USA
关键词
dopamine transporter; fast-scan cyclic voltammetry; dopamine; amphetamine; uptake kinetics; uptake inhibition;
D O I
10.1046/j.1471-4159.1999.0732406.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The dopamine (DA) transporter (DAT) regulates DA neurotransmission by recycling DA back into neurons. Drugs that interfere with DAT function, e.g., cocaine and amphetamine, can have profound behavioral effects. The kinetics of DA transport by DAT in isolated synaptosomal or single cell preparations have been previously studied. To investigate how DA transport is regulated in intact tissue and to examine how amphetamine affects the DAT, the kinetics of DA uptake by the DAT were examined in tissue slices of the mouse caudate-putamen with fast-scan cyclic voltammetry. The data demonstrate that inward DA transport is saturable and sodium-dependent. Elevated levels of cytoplasmic DA resulting from disruption of vesicular storage by incubation with 10 mu M Ro 4-1284 did not generate DA efflux or decrease its uptake rate. However, incubation with 10 mu M amphetamine reduced the net DA uptake rate and increased extracellular DA levels due to DA efflux through the DAT. In addition, a new, elevated steady-state level of extracellular DA was established after electrically stimulated DA release in the presence of amphetamine, norepinephrine, and exogenous DA, These results from intact tissue are consistent with a kinetic model of the DAT established in more purified preparations in which amphetamine and other transported substances make the inwardly facing DAT available for outward transport of intracellular DA.
引用
收藏
页码:2406 / 2414
页数:9
相关论文
共 53 条
[1]   MECHANISM OF TRANSPORT AND STORAGE OF BIOGENIC AMINES .3. EFFECTS OF SODIUM AND POTASSIUM ON KINETICS OF 5-HYDROXYTRYPTAMINE AND NOREPINEPHRINE TRANSPORT BY RABBIT SYNAPTOSOMES [J].
BOGDANSKI, DF ;
TISSARI, AH ;
BRODIE, BB .
BIOCHIMICA ET BIOPHYSICA ACTA, 1970, 219 (01) :189-+
[2]   Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine transporter [J].
Bosse, R ;
Fumagalli, F ;
Jaber, M ;
Giros, B ;
Gainetdinov, RR ;
Wetsel, WC ;
Missale, C ;
Caron, MG .
NEURON, 1997, 19 (01) :127-138
[3]  
Bunin MA, 1998, METHOD ENZYMOL, V296, P689
[4]   Human norepinephrine transporter kinetics using rotating disk electrode voltammetry [J].
Burnette, WB ;
Bailey, MD ;
Kukoyi, S ;
Blakely, RD ;
Trowbridge, CG ;
Justice, JB .
ANALYTICAL CHEMISTRY, 1996, 68 (17) :2932-2938
[5]  
Chen NH, 1998, J NEUROCHEM, V71, P653
[6]   ESTIMATION OF FREE DOPAMINE IN THE CYTOPLASM OF THE GIANT DOPAMINE CELL OF PLANORBIS-CORNEUS BY VOLTAMMETRY AND CAPILLARY ELECTROPHORESIS [J].
CHIEN, JB ;
WALLINGFORD, RA ;
EWING, AG .
JOURNAL OF NEUROCHEMISTRY, 1990, 54 (02) :633-638
[7]  
COLZI A, 1993, J PHARMACOL EXP THER, V265, P103
[8]   Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter [J].
Erickson, JD ;
Schafer, MKH ;
Bonner, TI ;
Eiden, LE ;
Weihe, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (10) :5166-5171
[9]   INVIVO MECHANISMS UNDERLYING DOPAMINE RELEASE FROM RAT NIGROSTRIATAL TERMINALS .1. STUDIES USING VERATRINE AND OUABAIN [J].
FAIRBROTHER, IS ;
ARBUTHNOTT, GW ;
KELLY, JS ;
BUTCHER, SP .
JOURNAL OF NEUROCHEMISTRY, 1990, 54 (06) :1834-1843
[10]   EFFECT OF A RESERPINE-LIKE AGENT ON THE RELEASE AND METABOLISM OF [H-3] NA IN CELL-BODIES AND TERMINALS [J].
FILINGER, EJ .
GENERAL PHARMACOLOGY, 1994, 25 (05) :1039-1043