TRANSPORT OF METABOLIC SUBSTRATES THROUGH THE BLOOD‐BRAIN BARRIER 1
TRANSPORT OF METABOLIC SUBSTRATES THROUGH THE BLOOD‐BRAIN BARRIER 1
复制标题
通过血脑屏障转运代谢底物 1
DOI：
10.1111/j.1471-4159.1977.tb07702.x
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发表时间：
1977
影响因子：
4.7
通讯作者：
W. Oldendorf
中科院分区：
文献类型：
--
作者：
W. Pardridge;W. Oldendorf
脑毛细血管的内皮细胞，像上皮细胞一样，在相邻细胞的质膜之间具有紧密连接（BRIGHTMAN等，1970年）。因此，脑内皮细胞的质膜在血液和脑血管之间形成连续的膜屏障。与其他细胞膜系统类似，循环物质通过血脑屏障（BBB）的通量通过（i）脂质介导或（ii）载体介导发生（OLDENDORF，1976）。在过去的十年中，随着组织取样、单次注射方法等新技术的引入（OLDENDORF，1970），获得了许多关于代谢底物通过BBB的载体介导转运的定量信息。最近已将由四种独立载体系统（己糖、中性氨基酸、碱性氨基酸和单羧酸）之一转运的底物的血浆浓度、转运Ki和VKi估计值制成表格（PARDRIDGE等人，1975年; OLDENWRF，1976年）。此外，最近还鉴定了四种其他独立的载体系统;这些系统介导核苷、嘌呤（CORNFORD & OLDENDORF，1975）、酸性氨基酸（OLDENDORF & SZABO，1976）和胆碱（OLDENDORF & BRAUN，1976）转运到脑中。表1中列出了8个独立的传输系统，相对于每个系统的V，估计值。如果假设每个载体以可比较的速率移动通过膜，则Vma，提供了BBB内的运输系统的冗余的量度。通常，随着屏障转运能力（Vi）降低，转运亲和力增加，如由降低的Ki表示的（表1）。代谢底物的BBB转运的非饱和组分在30倍范围内变化（表1），可能反映了通过极低亲和力、高容量系统或通过自由扩散的转运。
THE ENDOTHELIAL cells of cerebral capillaries, like epithelial cells, possess tight junctions between the plasmalemma of adjacent cells (BRIGHTMAN et al., 1970). As a consequence, the plasma membranes of brain endothelial cells form a continuous membranous barrier between blood and brain interstitium. Similar to other cell membrane systems, the flux of circulating substances through the blood-brain barrier (BBB) occurs, via either (i) lipid mediation, or (ii) carrier mediation (OLDENDORF, 1976). During the past decade with the introduction of newer techniques such as tissue sampling, single-injection methodology (OLDENDORF, 1970), much quantitative information has been obtained regarding the carrier-mediated transport of metabolic substrates through the BBB. Plasma concentrations, transport K,, and V,,, estimates for substrates transported by one of four independent carrier systems (hexose, neutral amino acid, basic amino acid and monocarboxylic acid) have been recently tabulated (PARDRIDGE et ul., 1975; OLDENWRF, 1976). In addition, four other independent carrier systems have recently been identified; these systems mediate the transport into brain of nucleosides, purines (CORNFORD & OLDENDORF, 1975), acidic amino acids (OLDENDORF & SZABO, 1976), and choline (OLDENDORF & BRAUN, 1976). The 8 independent transport systems are listed in Table 1 relative to the V,,, estimate for each system. If it is assumed that each carrier moves through the membrane at a comparable rate, then the Vma,,,provides a measure of the redundancy of the transport system within the BBB. Generally, as barrier transport capacity (V,,,) decreases, the transport affinity increases, as represented by decreasing K , (Table 1). The non-saturable component of BBB transport of metabolic substrates varies over a 30-fold range (Table 1) and probably reflects transport via either very low affinity, high capacity systems, or via free diffusion.