Characterization of the blood-brain barrier choline transporter using the in situ rat brain perfusion technique

被引:90
作者
Allen, DD
Smith, QR
机构
[1] Texas Tech Univ, Dept Pharmaceut Sci, Sch Pharm, HSC, Amarillo, TX 79106 USA
[2] NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA
关键词
acetylcholine; blood-brain barrier; cerebrovascular; choline; hemicholinium; transporter;
D O I
10.1046/j.1471-4159.2001.00093.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
Choline enters brain by saturable transport at the blood-brain barrier (BBB). In separate studies, both sodium-dependent and passive choline transport systems of differing affinity have been reported at brain capillary endothelial cells. In the present study, we re-examined brain choline uptake using the in situ rat brain perfusion technique. Saturable brain choline uptake from perfusion fluid was best described by a model with a single transporter (V(max) = 2.4-3.1 nmol/min/g; K(m) = 39-42 muM) With an apparent affinity (1/K(m)) for choline five to ten-fold greater than previously reported in vivo, but less than neuronal 'high-affinity' brain choline transport (K(m) = 1-5 muM) BBB choline uptake from a sodium-free perfusion fluid using sucrose for osmotic balance was 50% greater than in the presence of sodium suggesting that sodium is not required for transport. Hemicholinium-3 inhibited brain choline uptake with a K(i) (57 +/- 11 muM) greater than that at the neuronal choline system. In summary, BBB choline transport occurs with greater affinity than previously reported, but does not match the properties of the neuronal choline transporter. The V(max) of this system is appreciable and may provide a mechanism for delivering cationic drugs to brain.
引用
收藏
页码:1032 / 1041
页数:10
相关论文
共 44 条
  • [1] Blood-brain barrier choline transport in the senescent rat
    Allen, DD
    Smith, QR
    [J]. NEUROSCIENCE LETTERS, 1999, 277 (03) : 198 - 202
  • [2] HEMICHOLINIUM-3 BINDING-SITES IN RAT-BRAIN - A QUANTITATIVE AUTORADIOGRAPHIC STUDY
    BEKENSTEIN, JW
    WOOTEN, GF
    [J]. BRAIN RESEARCH, 1989, 481 (01) : 97 - 105
  • [3] HIGH AFFINITY CHOLINE TRANSPORT IN GUINEA-PIG BRAIN AND EFFECT OF NOREPINEPHRINE
    CARROLL, PT
    BUTERBAUGH, GG
    [J]. JOURNAL OF NEUROCHEMISTRY, 1975, 24 (05) : 917 - 924
  • [4] ACTIVE-TRANSPORT OF BUTYROBETAINE AND CARNITINE INTO ISOLATED LIVER-CELLS
    CHRISTIANSEN, RZ
    BREMER, J
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1976, 448 (04) : 562 - 577
  • [5] DECREASED BRAIN CHOLINE UPTAKE IN OLDER ADULTS - AN IN-VIVO PROTON MAGNETIC-RESONANCE SPECTROSCOPY STUDY
    COHEN, BM
    RENSHAW, PF
    STOLL, AL
    WURTMAN, RJ
    YURGELUNTODD, D
    BABB, SM
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1995, 274 (11): : 902 - 907
  • [6] COOPER JR, 1994, J NEUROCHEM, V63, P395
  • [7] CARRIER MEDIATED BLOOD-BRAIN-BARRIER TRANSPORT OF CHOLINE AND CERTAIN CHOLINE ANALOGS
    CORNFORD, EM
    BRAUN, LD
    OLDENDORF, WH
    [J]. JOURNAL OF NEUROCHEMISTRY, 1978, 30 (02) : 299 - 308
  • [8] DRAPER NR, 1981, APPL REGRESSION ANAL, P33
  • [9] DUCIS L, 1988, CHOLINERGIC SYNAPSE, P409
  • [10] CHOLINE UPTAKE BY CEREBRAL CAPILLARY ENDOTHELIAL-CELLS IN CULTURE
    ESTRADA, C
    BREADY, J
    BERLINER, J
    CANCILLA, PA
    [J]. JOURNAL OF NEUROCHEMISTRY, 1990, 54 (05) : 1467 - 1473