Permeability of the blood-brain barrier to a novel satiety molecule nesfatin-1.
Nesfatin-1 has recently been identified as a hypothalamic and brain stem peptide that regulates feeding behavior. Here, we determined the ability of nesfatin-1 to cross the blood-brain barrier (BBB) of mice. We used multiple-regression analysis to determine that radioactively labeled nesfatin-1 injected intravenously entered the brain. The entry rate (K(i)) of (131)I-nesfatin-1 from blood-to-brain was 0.20+/-0.02 microl/g min. This modest rate of entry was not inhibited by the administration of nonradioactive nesfatin-1, suggesting that BBB transport of nesfatin-1 into the brain is by a nonsaturable mechanism. High performance liquid chromatography (HPLC) and acid precipitation showed that most of the injected radiolabeled nesfatin-1 reached the brain as intact peptide, and capillary depletion with vascular washout revealed that 67% of (131)I-nesfatin-1 crossed the BBB to reach the brain parenchyma. Efflux of labeled nesfatin-1 from brain back into blood was by way of bulk flow. These findings demonstrate that nesfatin-1 crosses the BBB in both the blood-to-brain and brain-to-blood directions by nonsaturable mechanisms.
Price
Tulin O
TO
Geriatric Research, Education, and Clinical Center (GRECC), Veteran Affairs Medical Center, St. Louis, MO 63106, USA.
Samson
Willis K
WK
Niehoff
Michael L
ML
Banks
William A
WA
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000097:blood / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000097:blood / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009419:Nerve Tissue Proteins; D009479:Neuropeptides / Q000097:blood / Q000502:physiology*; D000080866:Nucleobindins; D010539:Permeability; D012528:Satiety Response / Q000502:physiology*
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins