Reith J, Dyve S, Kuwabara H, Guttman M, Diksic M, Gjedde A
McConnell Brain Imaging Center, Montreal Neurological Institute, Quebec, Canada.
J Cereb Blood Flow Metab. 1990 Sep;10(5):707-19. doi: 10.1038/jcbfm.1990.124.
In a study designed to reveal the rates of blood-brain transfer and decarboxylation of fluoro-L-3,4-dihydroxyphenylalanine (FDOPA), we discovered a major discrepancy between the DOPA decarboxylase activity reported in the literature and the rate of FDOPA decarboxylation measured in the study. "Donor" rats received intravenous injections of 6 mCi fluorine-18-labeled FDOPA. The donor rats synthesized methyl-FDOPA. Arterial plasma, containing both FDOPA and methyl-FDOPA, was sampled from the donor rats at different times and reinjected into "recipient" rats in which it circulated for 20 s. The blood-brain clearance of the mixture of labeled tracers in the plasma was determined by an integral method. The individual permeabilities were determined by linear regression analysis, according to which the average methyl-FDOPA permeability in the blood-brain barrier was twice that of FDOPA, which averaged 0.037 ml g-1 min-1. The permeability ratio was used to determine the fractional clearance from the brain of FDOPA (and hence of methyl-FDOPA), which averaged 0.081 min-1. In the striatum, the measured average FDOPA decarboxylation rate constant (kD3) was 0.010 min-1, or no more than 1% of the rate of striatal decarboxylation of DOPA measured in vitro and in vivo. We interpreted this finding as further evidence in favor of the hypothesis that striatum has two dopamine (DA) pools, of which only DA in the large pool is protected from metabolism. Hence, no more than 1% of the quantity of fluoro-DA theoretically synthesized was actually retained in striatum.
在一项旨在揭示氟代-L-3,4-二羟基苯丙氨酸（FDOPA）的血脑转运速率和脱羧作用的研究中，我们发现文献报道的多巴脱羧酶活性与本研究中测得的FDOPA脱羧速率之间存在重大差异。“供体”大鼠接受静脉注射6毫居里氟-18标记的FDOPA。供体大鼠合成了甲基-FDOPA。在不同时间从供体大鼠采集含有FDOPA和甲基-FDOPA的动脉血浆，并重新注入“受体”大鼠体内，使其循环20秒。通过积分法测定血浆中标记示踪剂混合物的血脑清除率。通过线性回归分析确定个体通透性，据此血脑屏障中甲基-FDOPA的平均通透性是FDOPA的两倍，FDOPA的平均通透性为0.037毫升·克⁻¹·分钟⁻¹。通透性比值用于确定FDOPA（以及甲基-FDOPA）从脑内的分数清除率，其平均值为0.081分钟⁻¹。在纹状体中，测得的平均FDOPA脱羧速率常数（kD3）为0.010分钟⁻¹，不超过体外和体内测得的纹状体多巴脱羧速率的1%。我们将这一发现解释为进一步支持以下假说的证据，即纹状体有两个多巴胺（DA）池，其中只有大池中 的DA受到代谢保护。因此，理论上合成的氟代-DA实际保留在纹状体中的量不超过1%。
