caa a22 4500 445888563 CHVBK 20180317145608.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00535-011-0438-2 doi (NATIONALLICENCE)springer-10.1007/s00535-011-0438-2 Daikenchuto (TU-100) ameliorates colon microvascular dysfunction via endogenous adrenomedullin in Crohn's disease rat model [Elektronische Daten] [Toru Kono, Yuji Omiya, Yoshiki Hira, Atsushi Kaneko, Shinichi Chiba, Tatsuya Suzuki, Masamichi Noguchi, Tsuyoshi Watanabe] Background: Daikenchuto (TU-100), a traditional Japanese medicine, has been reported to up-regulate the adrenomedullin (ADM)/calcitonin gene-related peptide (CGRP) system, which is involved in intestinal vasodilatation. The microvascular dysfunction of the intestine in Crohn's disease (CD), due to down-regulation of the ADM/CGRP system, is etiologically related to the recurrence of CD. Therefore, we investigated the vasodilatory effect of TU-100 in a CD rat model. Methods: Colitis was induced by the rectal instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. Laser Doppler blood flowmetry was used to measure colonic blood flow. ADM, CGRP, and their receptors in the ischemic colon were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme immunoassays. Additionally, we determined whether the intestinal epithelial cell line IEC-6 released ADM in response to TU-100. Results: TU-100 increased blood flow in ischemic segments of the colon but not in hyperemic segments. Pretreatment with an antibody to ADM abolished the vasodilatory effect of TU-100. CGRP levels and βCGRP mRNA expression were decreased in the ischemic colon, while protein and mRNA levels of ADM were unchanged. Hydroxy α-sanshool, the main constituent of TU-100, was the most active component in improving blood flow. Additionally, both TU-100 and hydroxy α-sanshool enhanced the release of ADM from IEC-6 cells. Conclusions: In the ischemic colon, endogenous βCGRP, but not ADM, was decreased. Thus, it was concluded that TU-100 ameliorated microvascular dysfunction by the up-regulation of endogenous ADM in the CD rat model. TU-100 may be a possible therapeutic agent for gastrointestinal ischemia-related diseases including CD. Springer, 2011 Daikenchuto (TU-100) nationallicence Adrenomedullin nationallicence Crohn's disease nationallicence Ischemia nationallicence Colonic blood flow nationallicence Kono Toru Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, 078-8510, Asahikawa, Hokkaido, Japan aut Omiya Yuji Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, 078-8510, Asahikawa, Hokkaido, Japan aut Hira Yoshiki Department of Anatomy, Asahikawa Medical University, Asahikawa, Hokkaido, Japan aut Kaneko Atsushi Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, 078-8510, Asahikawa, Hokkaido, Japan aut Chiba Shinichi Division of Central Laboratory for Research and Education, Asahikawa Medical University, Asahikawa, Hokkaido, Japan aut Suzuki Tatsuya Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, 078-8510, Asahikawa, Hokkaido, Japan aut Noguchi Masamichi Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan aut Watanabe Tsuyoshi Department of Anatomy, Asahikawa Medical University, Asahikawa, Hokkaido, Japan aut Journal of Gastroenterology Springer Japan 46/10(2011-10-01), 1187-1196 0944-1174 46:10<1187 2011 46 535 https://doi.org/10.1007/s00535-011-0438-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-011-0438-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kono Toru Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, 078-8510, Asahikawa, Hokkaido, Japan aut NATIONALLICENCE 700 1- Omiya Yuji Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, 078-8510, Asahikawa, Hokkaido, Japan aut NATIONALLICENCE 700 1- Hira Yoshiki Department of Anatomy, Asahikawa Medical University, Asahikawa, Hokkaido, Japan aut NATIONALLICENCE 700 1- Kaneko Atsushi Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, 078-8510, Asahikawa, Hokkaido, Japan aut NATIONALLICENCE 700 1- Chiba Shinichi Division of Central Laboratory for Research and Education, Asahikawa Medical University, Asahikawa, Hokkaido, Japan aut NATIONALLICENCE 700 1- Suzuki Tatsuya Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, 2-1 Midorigaoka-Higashi, 078-8510, Asahikawa, Hokkaido, Japan aut NATIONALLICENCE 700 1- Noguchi Masamichi Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan aut NATIONALLICENCE 700 1- Watanabe Tsuyoshi Department of Anatomy, Asahikawa Medical University, Asahikawa, Hokkaido, Japan aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/10(2011-10-01), 1187-1196 0944-1174 46:10<1187 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer