Gjedde A, Léger G C, Cumming P, Yasuhara Y, Evans A C, Guttman M, Kuwabara H
McConnell Brain Imaging Center, Montreal Neurological Institute, Quebec, Canada.
J Neurochem. 1993 Oct;61(4):1538-41. doi: 10.1111/j.1471-4159.1993.tb13651.x.
L-DOPA is a large neutral amino acid subject to transport out of, as well as into, brain tissue. Competition between dopamine synthesis and L-DOPA egress from striatum must favor L-DOPA egress if decarboxylation declines relatively more than transport in Parkinson's disease. To test this hypothesis, we injected patients with Parkinson's disease with a radiolabeled analogue of L-DOPA and recorded regional brain radioactivity as a function of time by means of positron emission tomography. We simultaneously estimated the activity of the decarboxylating enzyme and the amino acid transport. In the striatum of patients, we found the L-DOPA decarboxylase activity to be reduced in the head of the caudate nucleus and the putamen. However, the rate of egress of the DOPA analogue was unaffected by the disease and thus inhibited dopamine synthesis more than predicted in the absence of L-DOPA egress.
左旋多巴是一种大分子中性氨基酸,可进出脑组织。在帕金森病中,如果脱羧作用的下降相对超过转运作用,那么多巴胺合成与左旋多巴从纹状体流出之间的竞争必然有利于左旋多巴的流出。为了验证这一假设,我们给帕金森病患者注射了一种放射性标记的左旋多巴类似物,并通过正电子发射断层扫描记录了作为时间函数的脑区放射性。我们同时估计了脱羧酶的活性和氨基酸转运情况。在患者的纹状体中,我们发现尾状核头部和壳核中的左旋多巴脱羧酶活性降低。然而,多巴类似物的流出速率不受该疾病的影响,因此比在没有左旋多巴流出的情况下预测的更多地抑制了多巴胺合成。