Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier: relevance to neural disorders.
Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier: relevance to neural disorders.
复制标题
血脑屏障和血红脊髓液屏障的鸟可以化合物的转运特性：与神经疾病有关。
DOI：
10.1186/2045-8118-8-13
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发表时间：
2011-02-28
影响因子：
7.3
通讯作者：
Hosoya K
中科院分区：
文献类型：
--
作者：
Tachikawa M;Hosoya K
鸟嘌呤类化合物（GCs），如肌酸、磷酸肌酸、鸟嘌呤乙酸、肌酸酐、甲基鸟嘌呤、鸟嘌呤丁二酸、γ-鸟嘌呤丁酸、β-鸟嘌呤丙酸、鸟嘌呤乙烷磺酸和α-鸟嘌呤戊二酸，存在于哺乳动物大脑中。虽然肌酸和磷酸肌酸在大脑的能量稳态中起重要作用，但GCs的积累可能引起癫痫放电和抽搐。本文综述了生理上重要的和/或神经毒性的GCs在生理和病理条件下是如何在大脑中分布的。血脑屏障（BBB）和血脑脊液（CSF）屏障（BCSFB）的GCs转运蛋白已成为脑内GCs分布的重要贡献者。血脑屏障上表达的肌酸转运蛋白（CRT/溶质载体（SLC） 6A8）调节脑内肌酸浓度，是循环血液向脑供应肌酸的主要途径。CRT可能是促进s -腺苷甲硫氨酸缺乏患者血-脑胍-醋酸酯转运的关键因素：胍-醋酸酯n -甲基转移酶，肌酸生物合成酶，导致脑内胍-醋酸酯蓄积。在BCSFB上表达的CRT、牛磺酸转运蛋白（TauT/SLC6A6）和有机阳离子转运蛋白（OCT3/SLC22A3）参与了脑脊液中胍乙酸或肌酐的外排转运。有趣的是，血脑屏障外排转运的GCs，包括胍丁酯和肌酐，是可以忽略不计的，尽管血脑屏障具有多种GCs合成前体的外排转运系统，如氨基酸和神经递质。相反，BCSFB是一个主要的脑gc清除系统。综上所述，血脑屏障和BCSFB的GCs转运似乎是脑内GCs水平的关键决定因素，转运特性的改变可能导致某些神经系统疾病患者脑内GCs分布异常。
Guanidino compounds (GCs), such as creatine, phosphocreatine, guanidinoacetic acid, creatinine, methylguanidine, guanidinosuccinic acid, γ-guanidinobutyric acid, β-guanidinopropionic acid, guanidinoethane sulfonic acid and α-guanidinoglutaric acid, are present in the mammalian brain. Although creatine and phosphocreatine play important roles in energy homeostasis in the brain, accumulation of GCs may induce epileptic discharges and convulsions. This review focuses on how physiologically important and/or neurotoxic GCs are distributed in the brain under physiological and pathological conditions. Transporters for GCs at the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) have emerged as substantial contributors to GCs distribution in the brain. Creatine transporter (CRT/solute carrier (SLC) 6A8) expressed at the BBB regulates creatine concentration in the brain, and represents a major pathway for supply of creatine from the circulating blood to the brain. CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters. Instead, the BCSFB functions as a major cerebral clearance system for GCs. In conclusion, transport of GCs at the BBB and BCSFB appears to be the key determinant of the cerebral levels of GCs, and changes in the transport characteristics may cause the abnormal distribution of GCs in the brain seen in patients with certain neurological disorders.