Characterisation of L-tryptophan transporters in human placenta: a comparison of brush border and basal membrane vesicles

被引:87
作者
Kudo, Y [1 ]
Boyd, CAR [1 ]
机构
[1] Univ Oxford, Dept Human Anat & Genet, Oxford OX1 3QX, England
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2001年 / 531卷 / 02期
关键词
D O I
10.1111/j.1469-7793.2001.0405i.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. The mechanisms responsible for L-tryptophan transport at both the maternal- and fetal-facing surfaces of the term placenta have been determined in isolated membrane vesicles as part of a study on placental indoleamine 2,3-dioxygenase, the L-tryptophan-catabolising enzyme recently shown to regulate fete-maternal immunology. 2. Brush border vesicle uptake of L-tryptophan is substantially into an osmotically active space. It is sodium independent and N-ethylmaleimide sensitive. Uptake of L-tryptophan, which is markedly stereospecific, has a K-m of 28.3 muM and V-max of 1.72 pmol (mg protein)(-1) s(-1) and is completely abolished by the L-system-specific substrate 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). These findings are in keeping with L-tryptophan transport being exclusively via system L (induced by the heterodimeric heavy chain of CD98 and system L-amino acid transporter-1 (LAT-1)). 1-Methyl-tryptophan (which is a known competitive inhibitor of indoleamine 2,3-dioxygenase) is a competitive inhibitor of L-tryptophan flux through this transport system (K-i = 113 mum). 3. Basal membrane transport of L-tryptophan is more complex. Uptake is slower than at the brush border and although, as in the brush border, uptake is sodium independent, it is less sensitive to N-ethylmaleimide. There is clear evidence that two systems contribute to basal membrane transport since BCH is (in sodium-free media) only a partial inhibitor whereas L-histidine and L-cysteine are fully effective. The simplest explanation of these and other findings is that the basal membrane possesses two systems, one of which is similar to that induced by the heavy chain of CD98 and system L-amino acid transporter-2 (LAT-2). The other appears to be system y(+)L since in the presence of BCH inhibition by L-leucine but not by L-lysine is sodium dependent. 4. These findings suggest the existence of non-identical carrier-mediated transport systems for L-tryptophan in brush border and basal membranes. This asymmetry may explain net transplacental transfer of this amino acid.
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页码:405 / 416
页数:12
相关论文
共 21 条
[1]   The binding specificity of amino acid transport system y(+)L in human erythrocytes is altered by monovalent cations [J].
Angelo, S ;
Irarrazabal, C ;
Deves, R .
JOURNAL OF MEMBRANE BIOLOGY, 1996, 153 (01) :37-44
[2]   Development and polarization of cationic amino acid transporters and regulators in the human placenta [J].
Ayuk, PTY ;
Sibley, CP ;
Donnai, P ;
D'Souza, S ;
Glazier, JD .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2000, 278 (06) :C1162-C1171
[3]   1-METHYL-DL-TRYPTOPHAN, BETA-(3-BENZOFURANYL)-DL-ALANINE (THE OXYGEN ANALOG OF TRYPTOPHAN), AND BETA-[3-BENZO(B)THIENYL]-DL-ALANINE (THE SULFUR ANALOG OF TRYPTOPHAN) ARE COMPETITIVE INHIBITORS FOR INDOLEAMINE 2,3-DIOXYGENASE [J].
CADY, SG ;
SONO, M .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1991, 291 (02) :326-333
[4]  
Christensen H N, 1979, Adv Enzymol Relat Areas Mol Biol, V49, P41
[5]  
CHRISTENSEN HN, 1969, J BIOL CHEM, V244, P1510
[6]   Surface antigen CD98(4F2):: Not a single membrane protein, but a family of proteins with multiple functions [J].
Devés, R ;
Boyd, CAR .
JOURNAL OF MEMBRANE BIOLOGY, 2000, 173 (03) :165-177
[7]   MEMBRANE-POTENTIAL DEPENDENCE OF THE KINETICS OF CATIONIC AMINO-ACID-TRANSPORT SYSTEMS IN HUMAN PLACENTA [J].
ELENO, N ;
DEVES, R ;
BOYD, CAR .
JOURNAL OF PHYSIOLOGY-LONDON, 1994, 479 (02) :291-300
[8]   CHARACTERIZATION OF TRYPTOPHAN TRANSPORT IN HUMAN PLACENTAL BRUSH-BORDER MEMBRANE-VESICLES [J].
GANAPATHY, ME ;
LEIBACH, FH ;
MAHESH, VB ;
HOWARD, JC ;
DEVOE, LD ;
GANAPATHY, V .
BIOCHEMICAL JOURNAL, 1986, 238 (01) :201-208
[9]   ISOLATION AND PARTIAL CHARACTERIZATION OF THE BASAL-CELL MEMBRANE OF HUMAN PLACENTAL TROPHOBLAST [J].
KELLEY, LK ;
SMITH, CH ;
KING, BF .
BIOCHIMICA ET BIOPHYSICA ACTA, 1983, 734 (01) :91-98
[10]   Human placental indoleamine 2,3-dioxygenase: cellular localization and characterization of an enzyme preventing fetal rejection [J].
Kudo, Y ;
Boyd, CAR .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2000, 1500 (01) :119-124