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

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Jakub FichnaMartin Storr

Abstract

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-localized with NO synthase (NOS-1). In vitro, the TRPV4 agonist GSK1016790A reduced colonic contractility and increased inhibitory neurotransmission. In vivo, TRPV4 activation slowed GI motility and reduced stool production in mouse models mimicking pathophysiological conditions. We also showed that TRPV4 activation inhibited GI motility by reducing NO-dependent Ca(2+) release from enteric neurons. In conclusion, TRPV4 is involved in the regulation of GI motility in health and disease. • Recent studies implicate TRPV4 in pain signaling and intestinal inflamm...Continue Reading

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Citations

Oct 27, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Friedrich C Luft
Oct 7, 2017·Experimental & Molecular Medicine·Jing-Jing WanXia Liu
Sep 9, 2017·Alimentary Pharmacology & Therapeutics·A B BeckersD Keszthelyi
Oct 26, 2018·British Journal of Pharmacology·John L Wallace
Aug 15, 2018·Toxins·Brett BoonenKarel Talavera
Jun 20, 2021·Autonomic Neuroscience : Basic & Clinical·Kenton M Sanders, Violeta N Mutafova-Yambolieva
Sep 11, 2021·Cellular and Molecular Gastroenterology and Hepatology·Jackson L K YipElisa L Hill-Yardin

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