Permeability of porcine blood brain barrier to somatostatin analogues

被引:40
作者
Fricker, G [1 ]
Nobmann, S
Miller, DS
机构
[1] Heidelberg Univ, Inst Pharmazeut Technol & Biopharm, INF 366, D-69120 Heidelberg, Germany
[2] NIEHS, NIH, Res Triangle Pk, NC 27709 USA
关键词
blood brain barriers; cancer; central nervous system; confocal microscopy; Mrp2; octreotide; p-glycoprotein; somatostatin;
D O I
10.1038/sj.bjp.0704557
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Transport of a fluorescent somatostatin analogue (NBD-octreotide) across freshly isolated functionally intact capillaries from porcine brain was visualized by confocal microscopy and quantitated by image analysis. 2 Luminal accumulation of NBD-octreotide showed all characteristics of specific and energy-dependent transport. Steady-state luminal fluorescence averaged 2-3 times cellular fluorescence and was reduced to cellular levels when metabolism was inhibited by NaCN. 3 The accumulation of NBD-octreotide in capillary lumens was inhibited in a concentration-dependent manner by unlabelled octreotide, by verapamil, PSC-833 and cyclosporin A, potent inhibitors of p-glycoprotein, and by leucotriene C-4, a strong modulator of Mrp2. Conversely, unlabelled octreotide reduced luminal accumulation of fluorescent BODIPY-verapanlil oil glycoprotein and of fluorescein-methotrexate, on Mrp2, None of the inhibitors used significantly reduced cellular accumulation of the fluorescent substrates. 4 Together, the data are consistent with octreotide being transported across the luminal membrane of porcine brain capillaries by both P-gp and Mrp2. providing further evidence that both transporters contribute substantially to the active barrier function of this endothelium. British Journal of Pharmacology (2002).
引用
收藏
页码:1308 / 1314
页数:7
相关论文
共 29 条
  • [1] Abbruscato TJ, 1997, J PHARMACOL EXP THER, V280, P402
  • [2] PERMEABILITY OF THE MURINE BLOOD-BRAIN-BARRIER TO SOME OCTAPEPTIDE ANALOGS OF SOMATOSTATIN
    BANKS, WA
    SCHALLY, AV
    BARRERA, CM
    FASOLD, MB
    DURHAM, DA
    CSERNUS, VJ
    GROOT, K
    KASTIN, AJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (17) : 6762 - 6766
  • [3] PEPTIDES AND THE BLOOD-BRAIN-BARRIER - LIPOPHILICITY AS A PREDICTOR OF PERMEABILITY
    BANKS, WA
    KASTIN, AJ
    [J]. BRAIN RESEARCH BULLETIN, 1985, 15 (03) : 287 - 292
  • [4] SATURABLE EFFLUX OF THE PEPTIDES RC-160 AND TYR-MIF-1 BY DIFFERENT PARTS OF THE BLOOD-BRAIN-BARRIER
    BANKS, WA
    KASTIN, AJ
    SAM, HM
    CAO, VT
    KING, B
    MANESS, LM
    SCHALLY, AV
    [J]. BRAIN RESEARCH BULLETIN, 1994, 35 (02) : 179 - 182
  • [5] BEGLEY DJ, 1992, PROG BRAIN RES, V91, P163
  • [6] CHIKHALE EG, 1995, J PHARMACOL EXP THER, V273, P298
  • [7] ENTERAL ABSORPTION OF OCTREOTIDE - ABSORPTION ENHANCEMENT BY POLYOXYETHYLENE-24-CHOLESTEROL ETHER
    DREWE, J
    FRICKER, G
    VONDERSCHER, J
    BEGLINGER, C
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1993, 108 (02) : 298 - 303
  • [8] CARRIER-MEDIATED TRANSPORT OF LABELED OXYTOCIN FROM BRAIN TO BLOOD
    DURHAM, DA
    BANKS, WA
    KASTIN, AJ
    [J]. NEUROENDOCRINOLOGY, 1991, 53 (05) : 447 - 452
  • [9] Dutour A, 1998, INT J CANCER, V76, P620, DOI 10.1002/(SICI)1097-0215(19980529)76:5<620::AID-IJC2>3.3.CO
  • [10] 2-X