Title
Transient receptor potential vanilloid 4 inhibits mouse colonic motility by activating NO-dependent enteric neurotransmission Transient receptor potential vanilloid 4 inhibits mouse colonic motility by activating NO-dependent enteric neurotransmission
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Berlin ,
Subject
Human medicine
Source (journal)
Journal of molecular medicine. - Berlin
Volume/pages
93(2015) :12 , p. 1297-1309
ISSN
0946-2716
ISI
000365715300003
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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 Ca2+ release from enteric neurons. In conclusion, TRPV4 is involved in the regulation of GI motility in health and disease. aEuro cent aEuro integral Recent studies implicate TRPV4 in pain signaling and intestinal inflammation. aEuro cent aEuro integral Our aim was to characterize the role of TRPV4 in the control of GI motility. aEuro cent aEuro integral We found that TRPV4 activation reduced colonic contractility. aEuro cent aEuro integral Our studies also showed altered TRPV4 mRNA expression in IBS-C patients. aEuro cent aEuro integral TRPV4 may be a novel pharmacological target in functional GI diseases.
E-info
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https://repository.uantwerpen.be/docman/iruaauth/a5ab2f/130238.pdf
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