脑血管系统中大型中性氨基酸转运体（LAT1）亚型的主要功能活性。

Predominant functional activity of the large, neutral amino acid transporter (LAT1) isoform at the cerebrovasculature.

作者信息

Killian D M, Chikhale P J

机构信息

Department of Pharmaceutical Sciences, 20 North Pine Street, University of Maryland, Baltimore, MD 21201, USA.

出版信息

Neurosci Lett. 2001 Jun 22;306(1-2):1-4. doi: 10.1016/s0304-3940(01)01810-9.

DOI:10.1016/s0304-3940(01)01810-9

PMID:11403943

Abstract

In this study, we identify the predominant functional expression of the large, neutral amino acid transporter (LAT1) isoform at the blood-brain barrier (BBB). An in situ rat brain perfusion technique allowed perfusion of the radiotracer [(14)C]-L-Leu (a ligand for both LAT1 and LAT2) alone or competed with excess concentration of either LAT1 or LAT2 specific amino acids. The LAT2 specific amino acid, [(14)C]-L-Asn, was perfused alone or with excess concentration of various amino acids. The brain uptake of [(14)C]-L-Leu was not significantly inhibited by LAT2 specific amino acids, but was inhibited significantly (up to 90%) by the LAT1 specific amino acid, D-Met. L-Asn did not demonstrate saturable brain uptake. These data clearly demonstrate that LAT1 is the functionally predominant isoform expressed at the BBB which is responsible for brain uptake of large, neutral amino acids. In addition, the functional activity of cerebrovascular LAT2 is insignificant, or absent.

摘要

在本研究中，我们确定了大中性氨基酸转运体（LAT1）亚型在血脑屏障（BBB）处的主要功能表达。一种原位大鼠脑灌注技术允许单独灌注放射性示踪剂[(14)C]-L-亮氨酸（LAT1和LAT2的配体），或与过量的LAT1或LAT2特异性氨基酸竞争灌注。单独灌注LAT2特异性氨基酸[(14)C]-L-天冬酰胺，或与过量的各种氨基酸一起灌注。[(14)C]-L-亮氨酸的脑摄取未被LAT2特异性氨基酸显著抑制，但被LAT1特异性氨基酸D-蛋氨酸显著抑制（高达90%）。L-天冬酰胺未表现出可饱和的脑摄取。这些数据清楚地表明，LAT1是在血脑屏障处表达的功能上占主导地位的亚型，它负责大脑对大中性氨基酸的摄取。此外，脑血管LAT2的功能活性微不足道或不存在。