Characterization of blood-brain barrier permeability to PYY3-36 in the mouse.
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 microl/g-min, a rate similar to that previously measured for leptin. Influx was not inhibited by 1 microg/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.
Nonaka
Naoko
N
Oral Anatomy, School of Dentistry, Showa University, Tokyo, Japan.
Shioda
Seiji
S
Niehoff
Michael L
ML
Banks
William A
WA
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D004355:Drug Stability; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019894:Peptide YY / Q000493:pharmacokinetics*; D010539:Permeability
D019894:Peptide YY