Journal
PEPTIDES
Volume 28, Issue 12, Pages 2372-2381Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2007.10.008
Keywords
nesfatin-1; anorexigenic pepticle; blood-brain barrier; unidirectional influx rate
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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 I-131-nesfatin-1 from blood-to-brain was 0.20 +/- 0.02 mu l/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 I-131-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. Published by Elsevier Inc.
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