{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T08:19:14Z","timestamp":1778833154707,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T00:00:00Z","timestamp":1430352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>The basic dipeptide, Trp\u2010His, was found to show an in vivo anti\u2010atherosclerotic effect when orally administered to apo E\u2010deficient mice. In addition, this dipeptide causes vasorelaxation in contracted rat aorta via suppression of intracellular Ca<jats:sup>2+<\/jats:sup> signaling cascades. In this study, we attempted to determine whether Trp\u2010His can be absorbed after single oral administration in Sprague\u2013Dawley (SD) rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Trp\u2010His and His\u2010Trp (10 or 50 mg\/kg) was orally administered to 8\u2010week\u2010old male SD rats. Both peptides in plasma were assayed by LC\u2010MS\/MS in combination with 2,4,6\u2010trinitrobenzene sulfonate derivatization technique. In vitro transport experiments using Caco\u20102 cell monolayers were performed to evaluate the apparent permeability (<jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub>). A phytic acid\u2010aided MALDI\u2010MS imaging (MSI) was conducted to visualize the distribution of dipeptides in the rat intestinal membrane. Trp\u2010His was absorbed intact into SD rat blood, showing a maximal level at 1 h after administration at 10 mg\/kg dose (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 28.7 \u00b1 8.9 pmol\/mL\u2010plasma; area under the curve, 71.3 \u00b1 18.7 pmol\u00b7h\/mL\u2010plasma). In contrast, His\u2010Trp was surprisingly not detected, although the <jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub> was compatible to that of Trp\u2010His. MSI analysis provided crucial evidence that Trp\u2010His was visualized in the overall intestinal membrane. The Trp\u2010His peptide was not visualized in the presence of Gly\u2010Sar, which is a model peptide that is transported via the intestinal proton\u2010coupled peptide transporter 1 (PepT1) transporter. The His\u2010Trp molecular ion was not observed at the intestinal membrane. The MSI analysis illustrated that there is no absorption of His\u2010Trp due to its unexpected hydrolysis by brush border proteases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>To the best of our knowledge, this is the first study demonstrating that the vasoactive Trp\u2010His is preferably transported across the rat intestinal membrane by PepT1 and is absorbed intact into the circulation. However, no absorption of His\u2010Trp, a reverse sequence of absorbable Trp\u2010His, 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201500075","type":"journal-article","created":{"date-parts":[[2015,3,25]],"date-time":"2015-03-25T11:02:25Z","timestamp":1427281345000},"page":"1541-1549","source":"Crossref","is-referenced-by-count":41,"title":["Visualized absorption of anti\u2010atherosclerotic dipeptide, Trp\u2010His, in Sprague\u2013Dawley rats by LC\u2010MS and MALDI\u2010MS imaging analyses"],"prefix":"10.1002","volume":"59","author":[{"given":"Mitsuru","family":"Tanaka","sequence":"first","affiliation":[{"name":"Faculty of Agriculture Graduate School of Kyushu University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong\u2010Min","family":"Hong","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture Graduate School of Kyushu University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture Graduate School of Kyushu University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing\u2010Qiang","family":"Hu","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture Graduate School of Kyushu University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiro","family":"Matsui","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture Graduate School of Kyushu University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,4,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1001065"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/64.5.767"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2002.03628.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/137.4.953"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf300497p"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1101-4"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.110.034025"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.80473"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf405639w"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac400294q"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.130448"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2011.02.037"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac402252j"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114509991814"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fob.2014.10.008"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2008.02.001"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088975"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fob.2012.04.005"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2014.07.020"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2012.12.026"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.109.116228"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf100388w"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf703640p"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2003.10.001"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3502"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1980.90"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3382\/ps.2012-02826"}],"container-title":["Molecular Nutrition &amp; 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