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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Characterization of Blood-Brain Barrier Permeability to PYY3-36 in the Mouse

Naoko Nonaka, Seiji Shioda, Michael L. Niehoff and William A. Banks
Journal of Pharmacology and Experimental Therapeutics September 2003, 306 (3) 948-953; DOI: https://doi.org/10.1124/jpet.103.051821
Naoko Nonaka
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Seiji Shioda
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Michael L. Niehoff
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William A. Banks
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Abstract

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 131I (I-PYY). Multiple-time regression analysis showed the unidirectional influx rate (Ki) from blood-to-brain for I-PYY to be 0.49 ± 0.19 μl/g-min, a rate similar to that previously measured for leptin. Influx was not inhibited by 1 μg/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.

Footnotes

  • This study was supported by VA merit review (to W.A.B.), R01 NS41863 (to W.A.B.), and R01 AA12743 (to W.A.B.).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • DOI: 10.1124/jpet.103.051821.

  • ABBREVIATIONS: NPY, neuropeptide Y; unlabeled PYY, unlabeled peptide YY3-36; BBB, blood-brain barrier; CNS, central nervous system; I-PYY, 131I-peptide YY3-36; Tc-Alb, 99mTc-albumin; LR, lactated Ringer's solution; HPLC, high-pressure liquid chromatography; TFA, trifluoroacetic acid; %Inj/ml, percentage of the injected dose present in a milliliter of serum.

    • Received March 18, 2003.
    • Accepted May 7, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 306 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 306, Issue 3
1 Sep 2003
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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Characterization of Blood-Brain Barrier Permeability to PYY3-36 in the Mouse

Naoko Nonaka, Seiji Shioda, Michael L. Niehoff and William A. Banks
Journal of Pharmacology and Experimental Therapeutics September 1, 2003, 306 (3) 948-953; DOI: https://doi.org/10.1124/jpet.103.051821

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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Characterization of Blood-Brain Barrier Permeability to PYY3-36 in the Mouse

Naoko Nonaka, Seiji Shioda, Michael L. Niehoff and William A. Banks
Journal of Pharmacology and Experimental Therapeutics September 1, 2003, 306 (3) 948-953; DOI: https://doi.org/10.1124/jpet.103.051821
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