FUNCTIONAL IDENTIFICATION AND MOLECULAR-CLONING OF A HUMAN BRAIN VESICLE MONOAMINE TRANSPORTER

被引：139

作者：

ERICKSON, JD

EIDEN, LE

机构：

[1] Section on Molecular Neuroscience, Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland

来源：

JOURNAL OF NEUROCHEMISTRY | 1993年 / 61卷 / 06期

关键词：

HUMAN VESICLE MONOAMINE TRANSPORTER TYPE-I; VACCINIA VIRUS SP6 BACTERIOPHAGE HYBRID EXPRESSION; DIGITONIN PERMEABILIZATION; RESERPINE; TETRABENAZINE; BIOGENIC AMINES; MPP(+);

D O I：

10.1111/j.1471-4159.1993.tb07476.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A vesicle monoamine transporter was functionally identified, molecularly cloned, and characterized from a human substantia nigra cDNA library. The ATP-dependent transport of 5-[H-3]hydroxytryptamine ([H-3]5-HT) by digitonin-permeabilized fibroblasts expressing the vesicle monoamine/H+ antiporter in culture exhibited a K(m) of 0,55 muM. Reserpine and tetrabenazine, inhibitors of two monoamine binding sites, effectively blocked [H-3]5-HT accumulation with K(i) values of 34 and 78 nM, respectively. Pretreatment of cells with as little as 1 0 nM reserpine in the presence of ATP abolished uptake. The rank order for substrate inhibition of [H-3]5-HT uptake for both the previously reported rat vMAT1 and the human transporter clone followed the order 5-HT > dopamine > epinephrine > norepinephrine > 1 -methyl-4-phenylpyridinium > 2-phenylethylamine > histamine. The virtually identical transport characteristics of rvMAT1 and hvMAT1 confirm the relevance of neuropharmacological studies of rat brain biogenic amine uptake and storage to human brain neurochemistry.

引用

页码：2314 / 2317

页数：4

共 17 条

[1] THE CAENORHABDITIS-ELEGANS UNC-17 GENE - A PUTATIVE VESICULAR ACETYLCHOLINE TRANSPORTER [J].

ALFONSO, A ;

GRUNDAHL, K ;

DUERR, JS ;

HAN, HP ;

RAND, JB .

SCIENCE, 1993, 261 (5121) :617-619

[2]

CARLSSON A, 1966, ACTA PHARMACOL TOX, V24, P112

[3] RESERPINE BINDING TO CHROMAFFIN GRANULES SUGGESTS THE EXISTENCE OF 2 CONFORMATIONS OF THE MONOAMINE TRANSPORTER [J].

DARCHEN, F ;

SCHERMAN, D ;

HENRY, JP .

BIOCHEMISTRY, 1989, 28 (04) :1692-1697

[4] EXPRESSION CLONING OF A RESERPINE-SENSITIVE VESICULAR MONOAMINE TRANSPORTER [J].

ERICKSON, JD ;

EIDEN, LE ;

HOFFMAN, BJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (22) :10993-10997

[5]

ERICKSON JD, 1993, J NEUROCHEM, V61, pS24

[6] EUKARYOTIC TRANSIENT-EXPRESSION SYSTEM BASED ON RECOMBINANT VACCINIA VIRUS THAT SYNTHESIZES BACTERIOPHAGE-T7 RNA-POLYMERASE [J].

FUERST, TR ;

NILES, EG ;

STUDIER, FW ;

MOSS, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (21) :8122-8126

[7] MOLECULAR PHARMACOLOGY OF THE MONOAMINE TRANSPORTER OF THE CHROMAFFIN GRANULE MEMBRANE [J].

HENRY, JP ;

GASNIER, B ;

ROISIN, MP ;

ISAMBERT, MF ;

SCHERMAN, D .

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1987, 493 :194-206

[8] TRANSPORT OF 5-HYDROXYTRYPTAMINE IN MEMBRANE-VESICLES FROM RAT BASOPHILIC LEUKEMIA-CELLS [J].

KANNER, BI ;

BENDAHAN, A .

BIOCHIMICA ET BIOPHYSICA ACTA, 1985, 816 (02) :403-410

[9] A CDNA THAT SUPPRESSES MPP+ TOXICITY ENCODES A VESICULAR AMINE TRANSPORTER [J].

LIU, YJ ;

PETER, D ;

ROGHANI, A ;

SCHULDINER, S ;

PRIVE, GG ;

EISENBERG, D ;

BRECHA, N ;

EDWARDS, RH .

CELL, 1992, 70 (04) :539-551

[10] AMINE UPTAKE INTO INTACT MAST-CELL GRANULES INVITRO [J].

LUDOWYKE, RI ;

LAGUNOFF, D .

BIOCHEMISTRY, 1986, 25 (20) :6287-6293

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