Faull K F, Pascoe N, Maddaluno J, Greene K A, Wiener S G
Pasarow Analytical Neurochemistry Facility, Nancy Pritzker Laboratory of Behavioral Neurochemistry, Stanford University School of Medicine, California.
J Neurosci Res. 1990 Dec;27(4):533-40. doi: 10.1002/jnr.490270414.
In experimental protocols with humans and non-human primates, cerebrospinal fluid (CSF) concentrations of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the predominant end-product of norepinephrine metabolism in the mammalian central nervous system (CNS), have been widely used as an index of the rate of CNS norepinephrine metabolism. However, an earlier investigation showed that there was slow but free exchange between plasma and CSF MHPG. To define more precisely the time-course of equilibration of plasma and CSF MHPG, we intravenously administered 100 micrograms/kg of [2H3]-MHPG to drug-naive squirrel monkeys. Measurements were made of the concentrations of [2H3]- and [1H]-MHPG in plasma and cervical CSF samples collected at time points from 10 min to 4 hr thereafter. The results indicated that neither plasma nor CSF concentrations of [1H]-MHPG changed during the course of the experiment, and that [2H3]-MHPG appeared in the CSF within 10 min of intravenous administration. The maximal plasma and CSF concentrations of [2H3]-MHPG were 7.6- and 2.3-fold higher than the respective concentrations of [1H]-MHPG. The plasma and CSF pools of [2H3]-MHPG reached concentration equilibrium within 30 min, and thereafter the temporal decline in concentration of [2H3]-MHPG was the same in plasma and CSF. These results demonstrate that MHPG rapidly crosses from plasma to CSF, and support the suggestion that this factor be included in any attempts to estimate norepinephrine turnover in the CNS from measurements of steady-state MHPG concentrations in CSF or plasma.
在针对人类和非人类灵长类动物的实验方案中，3-甲氧基-4-羟基苯乙二醇（MHPG）是哺乳动物中枢神经系统（CNS）中去甲肾上腺素代谢的主要终产物，其脑脊液（CSF）浓度已被广泛用作中枢神经系统去甲肾上腺素代谢速率的指标。然而，一项早期研究表明，血浆和脑脊液中的MHPG之间存在缓慢但自由的交换。为了更精确地确定血浆和脑脊液中MHPG的平衡时间进程，我们给未接触过药物的松鼠猴静脉注射了100微克/千克的[2H3]-MHPG。在静脉注射后10分钟至4小时的时间点采集血浆和颈段脑脊液样本，测量其中[2H3]-和[1H]-MHPG的浓度。结果表明，在实验过程中，[1H]-MHPG的血浆和脑脊液浓度均未发生变化，且静脉注射后10分钟内[2H3]-MHPG就出现在了脑脊液中。[2H3]-MHPG的最大血浆浓度和脑脊液浓度分别比各自的[1H]-MHPG浓度高7.6倍和2.3倍。[2H3]-MHPG的血浆池和脑脊液池在30分钟内达到浓度平衡，此后[2H3]-MHPG浓度在血浆和脑脊液中的时间下降趋势相同。这些结果表明，MHPG能迅速从血浆进入脑脊液，并支持以下建议：在任何试图通过测量脑脊液或血浆中稳态MHPG浓度来估计中枢神经系统去甲肾上腺素周转率的尝试中，都应考虑这一因素。
