title: Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine.
abstract: The functional roles of transient receptor potential (TRP) channels in the gastrointestinal tract have garnered considerable attention in recent years. We previously reported that daikenchuto (TU-100), a traditional Japanese herbal medicine, increased intestinal blood flow (IBF) via adrenomedullin (ADM) release from intestinal epithelial (IE) cells (Kono T et al. J Crohns Colitis 4: 161-170, 2010). TU-100 contains multiple TRP activators. In the present study, therefore, we examined the involvement of TRP channels in the ADM-mediated vasodilatatory effect of TU-100. Rats were treated intraduodenally with the TRP vanilloid type 1 (TRPV1) agonist capsaicin (CAP), the TRP ankyrin 1 (TRPA1) agonist allyl-isothiocyanate (AITC), or TU-100, and jejunum IBF was evaluated using laser-Doppler blood flowmetry. All three compounds resulted in vasodilatation, and the vasodilatory effect of TU-100 was abolished by a TRPA1 antagonist but not by a TRPV1 antagonist. Vasodilatation induced by AITC and TU-100 was abrogated by anti-ADM antibody treatment. RT-PCR and flow cytometry revealed that an IEC-6 cell line originated from the small intestine and purified IE cells expressed ADM and TRPA1 but not TRPV1. AITC increased ADM release in IEC cells remarkably, while CAP had no effect. TU-100 and its ingredient 6-shogaol (6SG) increased ADM release dose-dependently, and the effects were abrogated by a TRPA1 antagonist. 6SG showed similar TRPA1-dependent vasodilatation in vivo. These results indicate that TRPA1 in IE cells may play an important role in controlling bowel microcirculation via ADM release. Epithelial TRPA1 appears to be a promising target for the development of novel strategies for the treatment of various gastrointestinal disorders.
authors.affiliation: Center for Clinical and Biomedical Research, Sapporo Hisgashi Tokushukai Hospital, Hokkaido, Japan. kono@asahikawa-med.ac.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Kono
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kaneko
authors.forename: Yuji
authors.initials: Y
authors.lastname: Omiya
authors.forename: Katsuya
authors.initials: K
authors.lastname: Ohbuchi
authors.forename: Nagisa
authors.initials: N
authors.lastname: Ohno
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D017879:Isothiocyanates; D007583:Jejunum / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D005894:Panax; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000819:agonists / Q000502:physiology*; D050916:TRPV Cation Channels / Q000819:agonists / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D032106:Zanthoxylum; D030521:Zingiberaceae
chemical_list: D017879:Isothiocyanates; D010936:Plant Extracts; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat; C121414:dai-kenchu-to; D053607:Adrenomedullin; C004471:allyl isothiocyanate; D002211:Capsaicin