Cumming P, Kuwabara H, Ase A, Gjedde A
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
J Neurochem. 1995 Sep;65(3):1381-90. doi: 10.1046/j.1471-4159.1995.65031381.x.
To test the hypothesis that L-DOPA decarboxylase (DDC) is a regulated enzyme in the synthesis of dopamine (DA), we developed a model of the cerebral uptake and metabolism of [3H]DOPA. The unidirectional blood-brain clearance of [3H]DOPA (K1D) was 0.049 ml g-1 min-1. The relative DDC activity (k3D) was 0.26 min-1 in striatum, 0.04 min-1 in hypothalamus, and 0.02 min-1 in hippocampus. In striatum, 3,4-[3H]dihydroxyphenylacetic acid ([3H]DOPAC) was formed from [3H]DA with a rate constant of 0.013 min-1, [3H]homovanillic acid ([3H]HVA) was formed from [3H]DOPAC at a rate constant of 0.020 min-1, and [3H]HVA was eliminated from brain at a rate constant of 0.037 min-1. Together, these rate constants predicted the ratios of endogenous DOPAC and HVA to DA in rat striatum. Pargyline, an inhibitor of DA catabolism, substantially reduced the contrast between striatum and cortex, in comparison with the contrast seen in autoradiograms of control rats. At 30 min and at 4 h after pargyline, k3D was reduced by 50% in striatum and olfactory tubercle but was unaffected in hypothalamus, indicating that DDC activity is reduced in specific brain regions after monoamine oxidase inhibition. Thus, DDC activity may be a regulated step in the synthesis of DA.
为了验证左旋多巴脱羧酶（DDC）是多巴胺（DA）合成过程中一种受调控的酶这一假说，我们建立了一个[3H]多巴在大脑中摄取和代谢的模型。[3H]多巴的单向血脑清除率（K1D）为0.049 ml g-1 min-1。纹状体中相对DDC活性（k3D）为0.26 min-1，下丘脑为0.04 min-1，海马体为0.02 min-1。在纹状体中，[3H]多巴胺（[3H]DA）形成3,4-[3H]二羟基苯乙酸（[3H]DOPAC）的速率常数为0.013 min-1，[3H]DOPAC形成[3H]高香草酸（[3H]HVA）的速率常数为0.020 min-1，[3H]HVA从大脑中消除的速率常数为0.037 min-1。这些速率常数共同预测了大鼠纹状体内内源性DOPAC和HVA与DA的比例。与对照大鼠放射自显影片中的对比度相比，多巴胺分解代谢抑制剂帕吉林显著降低了纹状体与皮质之间的对比度。在帕吉林给药后30分钟和4小时，纹状体和嗅结节中的k3D降低了50%，但下丘脑未受影响，这表明单胺氧化酶抑制后特定脑区的DDC活性降低。因此，DDC活性可能是多巴胺合成过程中的一个受调控步骤。
