Dethy S, Laute M A, Damhaut P, Goldman S
Service de Neurologie, ULB-Hôpital Erasme, Brussels, Belgium.
J Neural Transm (Vienna). 1999;106(2):145-58. doi: 10.1007/s007020050147.
We used intrastriatal microdialysis to study the effect of pergolide, a D1/D2 dopamine (DA) receptor agonist on biotransformation of exogenous L-DOPA in hemi-Parkinsonian rats. DA and metabolites were assayed by microbore liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 67% and 87% decrease in striatal EC levels of DA in intact and denervated striatum respectively. In intact striatum but not in denervated striatum, pergolide decreased EC levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) (53% and 42% decrease, respectively). L-DOPA (100 mg/kg, i.p.) produced significant increase in EC levels of DA, DOPAC and HVA in intact and denervated striatum with and without local perfusion of 10(-4) M pergolide. In denervated striatum, L-DOPA-induced DA increase was significantly higher in rats with pergolide. Our results suggest that, in an animal model of Parkinson's disease, pergolide in association with L-DOPA favors the restoration of striatal EC DA levels.
我们采用纹状体内微透析技术,研究了D1/D2多巴胺(DA)受体激动剂培高利特对偏侧帕金森病大鼠中外源性左旋多巴生物转化的影响。通过微径液相色谱法测定DA及其代谢产物。培高利特(50微克/千克,腹腔注射)使完整纹状体和去神经支配纹状体中DA的纹状体细胞外(EC)水平分别下降了67%和87%。在完整纹状体而非去神经支配纹状体中,培高利特降低了3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)的EC水平(分别下降53%和42%)。左旋多巴(100毫克/千克,腹腔注射)在完整和去神经支配的纹状体中,无论是否局部灌注10^(-4) M培高利特,均使DA、DOPAC和HVA的EC水平显著升高。在去神经支配的纹状体中,培高利特处理的大鼠中左旋多巴诱导的DA升高显著更高。我们的结果表明,在帕金森病动物模型中,培高利特与左旋多巴联合使用有利于恢复纹状体EC DA水平。