TY - JOUR T1 - Characterization of Blood-Brain Barrier Permeability to PYY<sub>3-36</sub> in the Mouse JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 948 LP - 953 DO - 10.1124/jpet.103.051821 VL - 306 IS - 3 AU - Naoko Nonaka AU - Seiji Shioda AU - Michael L. Niehoff AU - William A. Banks Y1 - 2003/09/01 UR - http://jpet.aspetjournals.org/content/306/3/948.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -