Pritchard J B
J Pharmacol Exp Ther. 1980 Feb;212(2):354-9.
In this study, two questions were addressed: 1) were anionic pesticides accumulated by choroid plexus via the organic acid transport system and 2) did such accumulation impair transport of anionic neurotransmitter metabolites normally eliminated from brain via this system? Rabbit lateral choroid plexi were incubated in Krebs-Ringer bicarbonate buffer in vitro with the herbicide, 2,4-dichlorophenoxyacetic acid, or the polar DDT metabolite, 2,2-bis (p-chlorophenyl)acetic acid (DDA). Both compounds were extensively accumulated. At a pesticide concentration of 1 microM, tissue-to-medium ratios of 40 (DDA) to 50 (2,4-dichlorophenoxyacetic acid) were found after 60-min incubation at 37 degrees C. Uptake of both compounds was energy- and concentration-dependent and could be inhibited by other organic anions. 2,4-Dichlorophenoxyacetic acid and DDA each produced dose-dependent inhibition of the uptake of the other pesticide. DDA was the more potent inhibitor. Thus, uptake of both compounds appeared to be mediated by the organic acid transport system. Furthermore, transport of the serotonin metabolite, 5-hydroxy-3-indole-acetic acid was more effectively inhibited by these pesticides than by the classical inhibitor, probenecid. Neither the parent amine, serotonin, nor the uncharged pesticides. DDT and dieldrin, inhibited 5-hydroxy-3-indole-acetic acid uptake. Thus, the effect appears specific for those compounds which share the organic anion transport system.
在本研究中，探讨了两个问题：1）脉络丛是否通过有机酸转运系统积累阴离子农药？2）这种积累是否会损害通常通过该系统从大脑中清除的阴离子神经递质代谢物的转运？兔外侧脉络丛在体外于Krebs-Ringer碳酸氢盐缓冲液中与除草剂2,4-二氯苯氧乙酸或极性滴滴涕代谢物2,2-双（对氯苯基）乙酸（DDA）一起孵育。两种化合物都被大量积累。在37℃孵育60分钟后，在农药浓度为1微摩尔时，发现组织与培养基的比率为40（DDA）至50（2,4-二氯苯氧乙酸）。两种化合物的摄取均依赖能量和浓度，并且可被其他有机阴离子抑制。2,4-二氯苯氧乙酸和DDA各自对另一种农药的摄取产生剂量依赖性抑制。DDA是更有效的抑制剂。因此，两种化合物的摄取似乎都是由有机酸转运系统介导的。此外，这些农药对血清素代谢物5-羟基-3-吲哚乙酸转运的抑制作用比经典抑制剂丙磺舒更有效。母体胺血清素和不带电荷的农药滴滴涕及狄氏剂均未抑制5-羟基-3-吲哚乙酸的摄取。因此，这种作用似乎对那些共享有机阴离子转运系统的化合物具有特异性。
