Transient receptor potential vanilloid 4 inhibits mouse colonic motility by activating NO-dependent enteric neurotransmission
| LEADER | caa a22 4500 | ||
|---|---|---|---|
| 001 | 605543240 | ||
| 003 | CHVBK | ||
| 005 | 20210128100925.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 210128e20151201xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.1007/s00109-015-1336-5 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00109-015-1336-5 | ||
| 245 | 0 | 0 | |a Transient receptor potential vanilloid 4 inhibits mouse colonic motility by activating NO-dependent enteric neurotransmission |h [Elektronische Daten] |c [J. Fichna, D. Poole, N. Veldhuis, S. MacEachern, D Saur, P. Zakrzewski, A. Cygankiewicz, A. Mokrowiecka, E. Małecka-Panas, W. Krajewska, W. Liedtke, M. Steinhoff, J-P. Timmermans, N. Bunnett, K. Sharkey, M. Storr] |
| 520 | 3 | |a 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. Key messages: • Recent studies implicate TRPV4 in pain signaling and intestinal inflammation. • Our aim was to characterize the role of TRPV4 in the control of GI motility. • We found that TRPV4 activation reduced colonic contractility. • Our studies also showed altered TRPV4 mRNA expression in IBS-C patients. • TRPV4 may be a novel pharmacological target in functional GI diseases. | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2015 | ||
| 690 | 7 | |a Irritable bowel syndrome |2 nationallicence | |
| 690 | 7 | |a Nitric oxide synthase type 1 |2 nationallicence | |
| 690 | 7 | |a Myenteric plexus |2 nationallicence | |
| 690 | 7 | |a 1400W : N-(3-Aminomethyl) benzylacetamidine, NOS-2 blocker |2 nationallicence | |
| 690 | 7 | |a EFS : Electrical field stimulation |2 nationallicence | |
| 690 | 7 | |a GFAP : Glial fibrillary acidic protein |2 nationallicence | |
| 690 | 7 | |a GSK1016790A : (N-((1S)-1-{[4-((2S)-2-{[(2,4-Dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide, TRPV4 agonist |2 nationallicence | |
| 690 | 7 | |a IBS : Irritable bowel syndrome |2 nationallicence | |
| 690 | 7 | |a LMMP : Longitudinal muscle-myenteric plexus |2 nationallicence | |
| 690 | 7 | |a NANC : Non-adrenergic, non-cholinergic |2 nationallicence | |
| 690 | 7 | |a ODQ : 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one,soluble guanylate cyclase inhibitor |2 nationallicence | |
| 690 | 7 | |a PTIO : 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide, NO scavenger |2 nationallicence | |
| 690 | 7 | |a RN 1734 : 2,4-Dichloro-N-isopropyl-N-(2-isopropylaminoethyl)benzenesulfonamide, TRPV4 antagonist |2 nationallicence | |
| 690 | 7 | |a RuR : Ruthenium red, TRPV antagonist |2 nationallicence | |
| 690 | 7 | |a SB 366791 : 4′-Chloro-3-methoxycinnamanilide, selective TRPV1 antagonist |2 nationallicence | |
| 690 | 7 | |a sGC : Soluble guanylate cyclase |2 nationallicence | |
| 690 | 7 | |a SMTC : S-Methyl-l-thiocitrulline, NOS-1 blocker |2 nationallicence | |
| 690 | 7 | |a TRPV4 : Transient receptor potential vanilloid type 4 |2 nationallicence | |
| 700 | 1 | |a Fichna |D J. |u Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada |4 aut | |
| 700 | 1 | |a Poole |D D. |u Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia |4 aut | |
| 700 | 1 | |a Veldhuis |D N. |u Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia |4 aut | |
| 700 | 1 | |a MacEachern |D S. |u Department of Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada |4 aut | |
| 700 | 1 | |a Saur |D D. |u II Medizinische Klinik, Technische Universität München, Munich, Germany |4 aut | |
| 700 | 1 | |a Zakrzewski |D P. |u Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland |4 aut | |
| 700 | 1 | |a Cygankiewicz |D A. |u Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland |4 aut | |
| 700 | 1 | |a Mokrowiecka |D A. |u Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, Lodz, Poland |4 aut | |
| 700 | 1 | |a Małecka-Panas |D E. |u Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, Lodz, Poland |4 aut | |
| 700 | 1 | |a Krajewska |D W. |u Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland |4 aut | |
| 700 | 1 | |a Liedtke |D W. |u Center for Translational Neuroscience, Duke University, Durham, NC, USA |4 aut | |
| 700 | 1 | |a Steinhoff |D M. |u Department of Dermatology and Surgery, University of California San Francisco, San Francisco, CA, USA |4 aut | |
| 700 | 1 | |a Timmermans |D J-P |u Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium |4 aut | |
| 700 | 1 | |a Bunnett |D N. |u Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia |4 aut | |
| 700 | 1 | |a Sharkey |D K. |u Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada |4 aut | |
| 700 | 1 | |a Storr |D M. |u Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada |4 aut | |
| 773 | 0 | |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/12(2015-12-01), 1297-1309 |x 0946-2716 |q 93:12<1297 |1 2015 |2 93 |o 109 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00109-015-1336-5 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00109-015-1336-5 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Fichna |D J. |u Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Poole |D D. |u Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Veldhuis |D N. |u Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a MacEachern |D S. |u Department of Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Saur |D D. |u II Medizinische Klinik, Technische Universität München, Munich, Germany |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Zakrzewski |D P. |u Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Cygankiewicz |D A. |u Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Mokrowiecka |D A. |u Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, Lodz, Poland |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Małecka-Panas |D E. |u Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, Lodz, Poland |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Krajewska |D W. |u Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Liedtke |D W. |u Center for Translational Neuroscience, Duke University, Durham, NC, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Steinhoff |D M. |u Department of Dermatology and Surgery, University of California San Francisco, San Francisco, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Timmermans |D J-P |u Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bunnett |D N. |u Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Sharkey |D K. |u Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Storr |D M. |u Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/12(2015-12-01), 1297-1309 |x 0946-2716 |q 93:12<1297 |1 2015 |2 93 |o 109 | ||