Visualized absorption of anti-atherosclerotic dipeptide, Trp-His, in Sprague-Dawley rats by LC-MS and MALDI-MS imaging analyses

Mitsuru Tanaka, Seong Min Hong, Sayaka Akiyama, Qing Qiang Hu, Toshiro Matsui

研究成果: ジャーナルへの寄稿記事

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Scope: The basic dipeptide, Trp-His, was found to show an in vivo anti-atherosclerotic effect when orally administered to apo E-deficient mice. In addition, this dipeptide causes vasorelaxation in contracted rat aorta via suppression of intracellular Ca2+ signaling cascades. In this study, we attempted to determine whether Trp-His can be absorbed after single oral administration in Sprague-Dawley (SD) rats. Methods and results: Trp-His and His-Trp (10 or 50 mg/kg) was orally administered to 8-week-old male SD rats. Both peptides in plasma were assayed by LC-MS/MS in combination with 2,4,6-trinitrobenzene sulfonate derivatization technique. In vitro transport experiments using Caco-2 cell monolayers were performed to evaluate the apparent permeability (Papp). A phytic acid-aided MALDI-MS imaging (MSI) was conducted to visualize the distribution of dipeptides in the rat intestinal membrane. Trp-His was absorbed intact into SD rat blood, showing a maximal level at 1 h after administration at 10 mg/kg dose (Cmax, 28.7 ± 8.9 pmol/mL-plasma; area under the curve, 71.3 ± 18.7 pmol·h/mL-plasma). In contrast, His-Trp was surprisingly not detected, although the Papp was compatible to that of Trp-His. MSI analysis provided crucial evidence that Trp-His was visualized in the overall intestinal membrane. The Trp-His peptide was not visualized in the presence of Gly-Sar, which is a model peptide that is transported via the intestinal proton-coupled peptide transporter 1 (PepT1) transporter. The His-Trp molecular ion was not observed at the intestinal membrane. The MSI analysis illustrated that there is no absorption of His-Trp due to its unexpected hydrolysis by brush border proteases. Conclusion: To the best of our knowledge, this is the first study demonstrating that the vasoactive Trp-His is preferably transported across the rat intestinal membrane by PepT1 and is absorbed intact into the circulation. However, no absorption of His-Trp, a reverse sequence of absorbable Trp-His, is observed owing to hydrolysis by intestinal proteases. This suggests that the bioavailability of peptides may be determined in part by their protease resistance in the intestinal membrane.

元の言語英語
ページ(範囲)1541-1549
ページ数9
ジャーナルMolecular Nutrition and Food Research
59
発行部数8
DOI
出版物ステータス出版済み - 1 1 2015

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All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science

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