Kim C S, Roe C R, Mann J D, Breese G R
Department of Neurology, University of North Carolina School of Medicine, Chapel Hill.
J Neurochem. 1992 Apr;58(4):1499-503. doi: 10.1111/j.1471-4159.1992.tb11370.x.
Effects of octanoic acid on monoamines and their acidic metabolites in the rat brain were analyzed by HPLC. Octanoic acid (1,000 mg/kg i.p.) elevated homovanillic acid levels by 54% in the caudate and 338% in the hypothalamus but increased 5-hydroxyindoleacetic acid (5-HIAA) levels in both the caudate and the hypothalamus by approximately 50% compared with the control. A lower dose of octanoic acid (500 mg/kg) increased 5-HIAA levels by 29% in the caudate and 20% in the hypothalamus. However, it did not produce any changes in the concentration of homovanillic acid in either the caudate or the hypothalamus. Treatment with octanoic acid also failed to change the level of dopamine, serotonin, and 3,4-dihydroxyphenylacetic acid in the caudate and the hypothalamus. The role of carrier-mediated transport in the clearance of 5-HIAA from the rabbit CSF was also evaluated in vivo by ventriculocisternal perfusion. Steady-state clearance of 5-HIAA from CSF exceeded that of inulin and was reduced in the presence of octanoic acid. Because this transport system in the choroid plexus is normally responsible for the excretion of the serotonin metabolite from the brain to the plasma, accumulation of endogenously produced organic acids in the brain, secondary to reduced clearance by the choroid plexus, could be a contributing factor in the development of encephalopathy in children with medium-chain acyl-CoA dehydrogenase deficiency who have elevated levels of octanoic acid systematically.
采用高效液相色谱法分析了辛酸对大鼠脑内单胺及其酸性代谢产物的影响。辛酸（腹腔注射1000mg/kg）使尾状核中高香草酸水平升高54%，下丘脑升高338%，但与对照组相比，尾状核和下丘脑的5-羟吲哚乙酸（5-HIAA）水平均升高约50%。较低剂量的辛酸（500mg/kg）使尾状核中5-HIAA水平升高29%，下丘脑升高20%。然而，它对尾状核或下丘脑中高香草酸的浓度没有产生任何变化。辛酸处理也未能改变尾状核和下丘脑中多巴胺、5-羟色胺和3,4-二羟基苯乙酸的水平。还通过脑室池灌注在体内评估了载体介导的转运在兔脑脊液中5-HIAA清除中的作用。脑脊液中5-HIAA的稳态清除率超过菊粉，且在辛酸存在时降低。由于脉络丛中的这种转运系统通常负责将5-羟色胺代谢产物从脑内排泄到血浆中，因此，对于中链酰基辅酶A脱氢酶缺乏且体内辛酸水平升高的儿童，脉络丛清除率降低继发脑内内源性有机酸蓄积可能是导致脑病的一个因素。
