Bromocriptine protects dopaminergic neurons from levodopa-induced toxicity by stimulating D2 receptors

被引：42

作者：

Takashima, H ^{[1
]}

Tsujihata, M

Kishikawa, M

Freed, WJ

机构：

[1] Nagasaki Kita Hosp, Neurol Sect, Nagasaki 8528061, Japan

[2] Aichi Human Serv Ctr, Dept Morphol, Aichi 4800392, Japan

[3] NIDA, IRP, Baltimore, MD 21224 USA

来源：

EXPERIMENTAL NEUROLOGY | 1999年 / 159卷 / 01期

关键词：

dopaminergic neurons; levodopa; neurotoxicity; neuroprotection; bromocriptine; D-2; receptor; agonist;

D O I：

10.1006/exnr.1999.7122

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Neuroprotective properties of bromocriptine, a D-2 receptor agonist, were investigated using the in vitro neurotoxicity of levodopa for dopaminergic neurons from rat embryonic ventral mesencephalon. Levodopa, when added to the culture medium, showed toxicity which was specific for dopaminergic neurons. Bromocriptine was found to protect dopaminergic neurons from levodopa toxicity. Another D-2 agonist, 2-(N-phenethyl-N-propyl-amino-5-hydroxytetralin, showed similar protective effects. The neuroprotective effect of bromocriptine was inhibited by supplementation of the culture medium with sulpiride, a D-2 antagonist, or by D-2 receptor knockdown with an antisense oligonucleotide. Dopaminergic neurons treated with levodopa showed an increase in free radicals. These data suggest that neuroprotective properties of bromocriptine seen in this cellular model of neurotoxicity are dependent on dopamine D-2 autoreceptor binding and that levodopa toxicity may be related to increased free radical generation in dopaminergic neurons. (C) 1999 Academic Press.

引用

页码：98 / 104

页数：7

共 58 条

[1] Comparison of neurotoxicity following repeated administration of L-dopa, D-dopa, and dopamine to embryonic mesencephalic dopamine neurons in cultures derived from Fisher 344 and Sprague-Dawley donors [J].

Alexander, T ;

Sortwell, CE ;

Sladek, CD ;

Roth, RH ;

SteeceCollier, K .

CELL TRANSPLANTATION, 1997, 6 (03) :309-315

[2]

AMINOFF MJ, 1994, WESTERN J MED, V161, P303

[3] MULTIPLE FLUORESCENT LIGANDS FOR DOPAMINE-RECEPTORS .2. VISUALIZATION IN NEURAL TISSUES [J].

ARIANO, MA ;

KANG, HC ;

HAUGLAND, RP ;

SIBLEY, DR .

BRAIN RESEARCH, 1991, 547 (02) :208-222

[4]

BERGAMASCO B, 1990, ACTA NEUROL SCAND, V81, P383

[5] SUPPRESSIVE EFFECT OF L-DOPA ON DOPAMINE CELLS REMAINING IN THE VENTRAL TEGMENTAL AREA OF RATS PREVIOUSLY EXPOSED TO THE NEUROTOXIN 6-HYDROXYDOPAMINE [J].

BLUNT, SB ;

JENNER, P ;

MARSDEN, CD .

MOVEMENT DISORDERS, 1993, 8 (02) :129-133

[6] 1-METHYL-4-PHENYLPYRIDINE IS NEUROTOXIC TO THE NIGROSTRIATAL DOPAMINE PATHWAY [J].

BRADBURY, AJ ;

COSTALL, B ;

DOMENEY, AM ;

JENNER, P ;

KELLY, ME ;

MARSDEN, CD ;

NAYLOR, RJ .

NATURE, 1986, 319 (6048) :56-57

[7] OPTIMIZED SURVIVAL OF HIPPOCAMPAL-NEURONS IN B27-SUPPLEMENTED NEUROBASAL(TM), A NEW SERUM-FREE MEDIUM COMBINATION [J].

BREWER, GJ ;

TORRICELLI, JR ;

EVEGE, EK ;

PRICE, PJ .

JOURNAL OF NEUROSCIENCE RESEARCH, 1993, 35 (05) :567-576

[8]

BUNNEY BS, 1973, J PHARMACOL EXP THER, V185, P560

[9] PRAMIPEXOLE, A DOPAMINE-D2 AUTORECEPTOR AGONIST, DECREASES THE EXTRACELLULAR CONCENTRATION OF DOPAMINE INVIVO [J].

CARTER, AJ ;

MULLER, RE .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 200 (01) :65-72

[10] Attenuation of levodopa-induced toxicity in mesencephalic cultures by pramipexole [J].

Carvey, PM ;

Pieri, S ;

Ling, ZD .

JOURNAL OF NEURAL TRANSMISSION, 1997, 104 (2-3) :209-228

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