Characterization of blood-brain barrier permeability to PYY3-36 in the mouse

被引:139
作者
Nonaka, N
Shioda, S
Niehoff, ML
Banks, WA
机构
[1] Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, John Cochran Div, St Louis, MO 63106 USA
[2] Showa Univ, Sch Dent, Tokyo 142, Japan
[3] Showa Univ, Sch Med, Tokyo 142, Japan
[4] St Louis Univ, Sch Med, Dept Internal Med, Div Geriatr, St Louis, MO USA
关键词
D O I
10.1124/jpet.103.051821
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Peptide YY3-36 (PYY) has emerged as an important signal in the gut-brain axis, with peripherally administered PYY affecting feeding and brain function. For these effects to be direct, PYY would have to cross the blood-brain barrier (BBB). Here, we determined the permeability of the BBB to PYY radioactively labeled with I-131 (I-PYY). Multiple-time regression analysis showed the unidirectional influx rate (K-i) from blood-to-brain for I-PYY to be 0.49 +/- 0.19 mul/g-min, a rate similar to that previously measured for leptin. Influx was not inhibited by 1 mug/mouse of unlabeled PYY, suggesting PYY crosses the BBB by transmembrane diffusion. About 0.176% of the i.v.-injected dose of I-PYY was taken up by brain, an amount similar to that for other peptides important in gut-brain communication. Capillary depletion showed that 69% of I-PYY crossed the BBB to enter the parenchymal space of the brain, and high-performance liquid chromatography demonstrated that the radioactivity in this space represented intact I-PYY. After intracerebroventricular injection, I-PYY crossed from brain to blood by the mechanism of bulk flow. We conclude that PYY crosses in both the blood-to-brain and brain-to-blood directions by nonsaturable mechanisms. Passage across the BBB provides a mechanism by which blood-borne PYY can affect appetite and brain function.
引用
收藏
页码:948 / 953
页数:6
相关论文
共 43 条
  • [1] Banks W A, 1993, Rev Neurosci, V4, P365
  • [2] PERMEABILITY OF THE BLOOD-BRAIN-BARRIER TO NEUROPEPTIDES - THE CASE FOR PENETRATION
    BANKS, WA
    KASTIN, AJ
    [J]. PSYCHONEUROENDOCRINOLOGY, 1985, 10 (04) : 385 - 399
  • [3] Passage of cytokines across the blood-brain barrier
    Banks, WA
    Kastin, AJ
    Broadwell, RD
    [J]. NEUROIMMUNOMODULATION, 1995, 2 (04) : 241 - 248
  • [4] BANKS WA, 1993, J PHARMACOL EXP THER, V267, P690
  • [5] Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure
    Banks, WA
    Tschöp, M
    Robinson, SM
    Heiman, ML
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2002, 302 (02) : 822 - 827
  • [6] PENETRATION OF INTERLEUKIN-6 ACROSS THE MURINE BLOOD-BRAIN-BARRIER
    BANKS, WA
    KASTIN, AJ
    GUTIERREZ, EG
    [J]. NEUROSCIENCE LETTERS, 1994, 179 (1-2) : 53 - 56
  • [7] Leptin enters the brain by a saturable system independent of insulin
    Banks, WA
    Kastin, AJ
    Huang, WT
    Jaspan, JB
    Maness, LM
    [J]. PEPTIDES, 1996, 17 (02) : 305 - 311
  • [8] Transport of insulin across the blood-brain barrier: Saturability at euglycemic doses of insulin
    Banks, WA
    Jaspan, JB
    Huang, WT
    Kastin, AJ
    [J]. PEPTIDES, 1997, 18 (09) : 1423 - 1429
  • [9] Differential transport of a secretin analog across the blood-brain and blood-cerebrospinal fluid barriers of the mouse
    Banks, WA
    Goulet, M
    Rusche, JR
    Niehoff, ML
    Boismenu, R
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2002, 302 (03) : 1062 - 1069
  • [10] Differential permeability of the blood-brain barrier to two pancreatic peptides: Insulin and amylin
    Banks, WA
    Kastin, AJ
    [J]. PEPTIDES, 1998, 19 (05) : 883 - 889