绵羊血脑屏障处L-苯丙氨酸及相关氨基酸的转运

Transport of L-phenylalanine and related amino acids at the ovine blood-brain barrier.

作者信息

Brenton D P, Gardiner R M

机构信息

Department of Paediatrics, University College London, Rayne Institute.

出版信息

J Physiol. 1988 Aug;402:497-514. doi: 10.1113/jphysiol.1988.sp017217.

DOI:10.1113/jphysiol.1988.sp017217

PMID:3236248

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1191904/

Abstract

Unidirectional influx of amino acids at the blood-brain barrier was studied in the lamb and sheep under barbiturate anaesthesia using the single-pass indicator-dilution technique. 2. In the lamb, influx of both L-phenylalanine (14 +/- 1 nmol g-1 min-1) and L-alanine (12 +/- 2 nmol g-1 min-1) was greater than in the sheep: L-phenylalanine influx, 9 +/- 1 nmol g-1 min-1; L-alanine influx, 5 +/- 1 nmol g-1 min-1 (P less than 0.01). This difference reflected higher blood concentrations of these amino acids in the younger animal. 3. The kinetic parameters of transport for L-phenylalanine were determined in the lamb and sheep from measurements of influx over a range of blood concentrations. The concentration dependence of L-phenylalanine influx was best described by a model with a saturable and non-saturable component. Maximum influx (Jmax) was higher and apparent transport constant (km, app) lower in the lamb. Values obtained (mean +/- S.E.M.) were: lamb, Jmax, 138 +/- 6 nmol g-1 min; km, app, 0.85 +/- 0.10 mmol l-1; sheep, Jmax, 107 +/- 7 nmol g-1 min-1; km, app, 2.25 +/- 0.25 mmol l-1. 4. L-Phenylalanine inhibited influx of L-leucine, L-tyrosine, L-valine and L-glutamine but not L-arginine and L-lysine. Its influx was inhibited by L-histidine, L-valine and L-leucine, but not by L-glutamine or L-alanine. In the lamb, L-phenylalanine inhibited L-histidine influx with an apparent inhibitor constant (kh) of 139 mumol l-1, and a maximum inhibition of 92%. In the sheep, L-phenylalanine inhibited L-methionine influx with an apparent kh of 33 mumol l-1 and a maximum inhibition of 82%. 5. Fractional extraction of phenylalanine and alanine was stereospecific with preference for the L-enantiomer. In the lamb, fractional extraction values (mean +/- S.E.M.) were: L-phenylalanine, 0.58 +/- 0.03; D-phenylalanine, 0.20 +/- 0.02; L-alanine, 0.16 +/- 0.03; D-alanine, 0.05 +/- 0.02. Self-inhibition of extraction was evident for L-phenylalanine and L-alanine in both lamb and sheep.

摘要

采用单通道指示剂稀释技术，在巴比妥类麻醉下的羔羊和绵羊中研究了血脑屏障处氨基酸的单向流入情况。2. 在羔羊中，L-苯丙氨酸（14±1 nmol g-1 min-1）和L-丙氨酸（12±2 nmol g-1 min-1）的流入量均高于绵羊：L-苯丙氨酸流入量为9±1 nmol g-1 min-1；L-丙氨酸流入量为5±1 nmol g-1 min-1（P＜0.01）。这种差异反映出幼龄动物中这些氨基酸的血液浓度较高。3. 通过在一系列血液浓度下测量流入量，测定了羔羊和绵羊中L-苯丙氨酸的转运动力学参数。L-苯丙氨酸流入量的浓度依赖性最好用一个具有饱和和非饱和成分的模型来描述。羔羊中的最大流入量（Jmax）较高，表观转运常数（km, app）较低。得到的值（平均值±标准误）为：羔羊，Jmax为138±6 nmol g-1 min；km, app为0.85±0.10 mmol l-1；绵羊，Jmax为107±7 nmol g-1 min-1；km, app为2.25±0.25 mmol l-1。4. L-苯丙氨酸抑制L-亮氨酸、L-酪氨酸、L-缬氨酸和L-谷氨酰胺的流入，但不抑制L-精氨酸和L-赖氨酸的流入。其流入受到L-组氨酸、L-缬氨酸和L-亮氨酸的抑制，但不受L-谷氨酰胺或L-丙氨酸的抑制。在羔羊中，L-苯丙氨酸抑制L-组氨酸流入，表观抑制剂常数（kh）为139 μmol l-1，最大抑制率为92%。在绵羊中，L-苯丙氨酸抑制L-甲硫氨酸流入，表观kh为33 μmol l-1，最大抑制率为82%。5. 苯丙氨酸和丙氨酸的分数提取具有立体特异性，优先选择L-对映体。在羔羊中，分数提取值（平均值±标准误）为：L-苯丙氨酸，0.58±0.03；D-苯丙氨酸，0.20±0.02；L-丙氨酸，0.16±0.03；D-丙氨酸，0.05±0.02。在羔羊和绵羊中，L-苯丙氨酸和L-丙氨酸的提取自抑制现象均明显。