Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine

Abstract

. 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.daikenchuto; TU-100; vasodilatation; 6-shogaol; inflammatory bowel diseases TRANSIENT RECEPTOR POTENTIAL (TRP) channels are nonselective calcium ion channels ubiquitously expressed in many tissues and are known to participate in a broad range of physical, chemical, and environmental stimuli such as taste, temperature, changes in osmolarity, pressure, stretch, and light.

Elevated H2O2 levels in trinitrobenzene sulfate‐induced colitis rats contributes to visceral hyperalgesia through interaction with the transient receptor potential ankyrin 1 cation channel

“…Reactive oxygen species, including H 2 O 2, are known to be upregulated in colorectal mucosa biopsies of active IBD patients and in TNBS‐induced rat colons . The infiltration of white blood cells or the presence of oxidative stress will cause the production of H 2 O 2 in mucosa and submucosa at an early stage of the TNBS model . Our data were consistent with these findings; we found that the content of H 2 O 2 increased 2.68‐fold in TNBS rats compared with the control rats.…”

“…Transient receptor potential ankyrin 1 has been suggested to be critical for visceral pain in IBD. TRPA1 is expressed abundantly in dorsal root ganglia (DRG) neurons innervating to the colon and on the epithelial cell of the intestine . TRPA1 was upregulated in the colon and DRG following experimental colitis .…”

Constipation and Herbal Medicine

“…Indeed, it was shown that the increased intestinal motility induced by Daikenchuto was inhibited by several serotonin receptor antagonists (Shibata et al, 1999;Satoh et al, 2001a,b). A recent study by Kono et al (2013) demonstrated that hydroxy-sanshools activate intestinal epithelial transient receptor potential cation channel, subfamily A, member 1 (TRPA1), which is highly expressed in enterochromaffin cells (serotonin-releasing cells), and may prove to be a novel target for constipation. In addition to the effects of these individual constituents, a recent study showed that Daikenchuto activates nicotinic acetylcholine receptors, which accounts for its effects on motility (Endo et al, 2014).…”

Clinical pharmacology of daikenchuto assessed by transit analysis using radiopaque markers in patients with colon cancer undergoing open surgery: a multicenter double-blind randomized placebo-controlled study (JFMC39-0902 additional study)

“…However, there are no previous reports of total and segmental transit analysis from the stomach to the anus using radiopaque markers after laparotomy. According to basic research on the use of DKT to regulate bowel activity [31,32], its action can be attributed to improvement in bowel blood flow, which in turn improves water absorption, and to protection against mucosal damage. Kono et al [33] found that DKT increased colonic vascular conductance, which was mainly mediated by calcitonin-gene-related peptide and its receptor components.…”