Journal article

Transient receptor potential vanilloid 4 inhibits mouse colonic motility by activating NO-dependent enteric neurotransmission

J Fichna, DP Poole, N Veldhuis, SJ MacEachern, D Saur, PK Zakrzewski, AI Cygankiewicz, A Mokrowiecka, E Malecka-Panas, WM Krajewska, W Liedtke, MS Steinhoff, J-P Timmermans, NW Bunnett, KA Sharkey, MA Storr

Journal of Molecular Medicine | SPRINGER HEIDELBERG | Published : 2015

Abstract

UNLABELLED: Recent studies implicate TRPV4 receptors in visceral pain signaling and intestinal inflammation. Our aim was to evaluate the role of TRPV4 in the control of gastrointestinal (GI) motility and to establish the underlying mechanisms. We used immunohistochemistry and PCR to study TRPV4 expression in the GI tract. The effect of TRPV4 activation on GI motility was characterized using in vitro and in vivo motility assays. Calcium and nitric oxide (NO) imaging were performed to study the intracellular signaling pathways. Finally, TRPV4 expression was examined in the colon of healthy human subjects. We demonstrated that TRPV4 can be found on myenteric neurons of the colon and is co-local..

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University of Melbourne Researchers

Grants

Awarded by Iuventus Plus program of the Polish Ministry of Science and Higher Education


Awarded by Medical University of Lodz


Awarded by National Science Centre


Awarded by NHMRC


Awarded by NIH


Awarded by Deutsche Forschungsgemeinschaft


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

The authors wish to thank Dr. Kevin Thorneloe (GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA) for providing GSK1016790A for this study, Wolfgang Liedtke (Duke University, Durham, NC, USA) for providing the TRPV4<SUP>-/-</SUP> mice, and Drs. Catherine Legraverend (Institut de Genomique Fonctionnelle, Montpellier, France) and Richard Dyck (University of Calgary, AB, Canada) for supplying the S100 beta-GFP mice. SJM was supported by the Dr. T. Chen Fong Doctoral Scholarship in Neuroscience through the Hotchkiss Brain Institute and a Studentship from Alberta Innovates-Health Solutions (AI-HS). KAS is the Crohn's and Colitis Foundation of Canada Chair in IBD Research. Supported by the Iuventus Plus program of the Polish Ministry of Science and Higher Education (0107/IP1/2013/72 to JF), Medical University of Lodz (503/1-156-04/503-01 to JF), National Science Centre (UMO-2013/11/B/NZ7/01301 and UMO-2014/13/B/NZ4/01179 to JF), NHMRC (454858 to DPP and 63303 to NWB), NIH (DK57840 to NWB), Monash University (to NWB), the Canadian Institutes of Health Research (to KAS), the Deutsche Forschungsgemeinschaft (STO 645/6-1 to MS), and the University of Calgary Research Grant Committee (to MS).