{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T02:37:22Z","timestamp":1789958242780,"version":"4.0.1"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study was conducted to investigate the effects of nitric oxide (NO) in acetic acid-induced gastric ulcer of rats and the underlying mechanisms. We found that peritoneal injection of sodium nitroprusside (SNP), a NO donor, decreased the ulcer area, inflammatory cell infiltration and MPO degree in acetic acid-induced gastric ulcer in rats. This effect was abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist or prior subdiaphragmatic vagotomy. SNP increased the jejunal mesenteric afferent discharge in a dose-depended manner, which was largely diminished by pretreatment of S-nitrosylation blocker N-ethylmaleimide, TRPV1 antagonist capsazepine, genetic deletion of TRPV1, or vagotomy. Whole-cell patch clamp recording showed that SNP depolarized the resting membrane potential of NG neurons, and enhanced capsaicin-induced inward current, which were both blocked by N-ethylmaleimide. Our results suggest that NO donor SNP alleviates acetic acid-induced gastric ulcer in rats via vagus nerve, while S-nitrosylation of TRPV1 may participate in this route. Our findings reveal a new mechanism for vagal afferent activation, and a new potential anti-inflammatory target.<\/jats:p>","DOI":"10.1038\/s41598-017-02275-1","type":"journal-article","created":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T15:53:53Z","timestamp":1494518033000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Nitric oxide donor protects against acetic acid-induced gastric ulcer in rats via S-nitrosylation of TRPV1 on vagus nerve"],"prefix":"10.1038","volume":"7","author":[{"given":"Ting","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8615-3897","authenticated-orcid":false,"given":"Chuanyong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,18]]},"reference":[{"key":"2275_CR1","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1126\/science.1281928","volume":"258","author":"JS Stamler","year":"1992","unstructured":"Stamler, J. S., Singel, D. J. & Loscalzo, J. Biochemistry of nitric oxide and its redox-activated forms. Science \n                           258, 1898\u20131902, doi:10.1126\/science.1281928 (1992).","journal-title":"Science"},{"key":"2275_CR2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/0896-6273(92)90104-L","volume":"8","author":"DS Bredt","year":"1992","unstructured":"Bredt, D. S. & Snyder, S. H. Nitric oxide, a novel neuronal messenger. Neuron \n                           8, 3\u201311, doi:10.1016\/0896-6273(92)90104-L (1992).","journal-title":"Neuron"},{"key":"2275_CR3","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1146\/annurev.ph.57.030195.003343","volume":"57","author":"J Garthwaite","year":"1995","unstructured":"Garthwaite, J. & Boulton, C. L. Nitric oxide signaling in the central nervous system. Annual review of physiology \n                           57, 683\u2013706, doi:10.1146\/annurev.ph.57.030195.003343 (1995).","journal-title":"Annual review of physiology"},{"key":"2275_CR4","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1136\/gutjnl-2011-301649","volume":"62","author":"JO Lundberg","year":"2013","unstructured":"Lundberg, J. O. & Weitzberg, E. Biology of nitrogen oxides in the gastrointestinal tract. Gut \n                           62, 616\u2013629, doi:10.1136\/gutjnl-2011-301649 (2013).","journal-title":"Gut"},{"key":"2275_CR5","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1053\/j.gastro.2003.11.046","volume":"126","author":"V Shah","year":"2004","unstructured":"Shah, V., Lyford, G., Gores, G. & Farrugia, G. Nitric oxide in gastrointestinal health and disease. Gastroenterology \n                           126, 903\u2013913, doi:10.1053\/j.gastro.2003.11.046 (2004).","journal-title":"Gastroenterology"},{"key":"2275_CR6","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1042\/bj3570593","volume":"357","author":"WK Alderton","year":"2001","unstructured":"Alderton, W. K., Cooper, C. E. & Knowles, R. G. Nitric oxide synthases: structure, function and inhibition. The Biochemical journal \n                           357, 593\u2013615, doi:10.1042\/bj3570593 (2001).","journal-title":"The Biochemical journal"},{"key":"2275_CR7","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1126\/science.1373522","volume":"256","author":"QW Xie","year":"1992","unstructured":"Xie, Q. W. et al. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science \n                           256, 225\u2013228, doi:10.1126\/science.1373522 (1992).","journal-title":"Science"},{"key":"2275_CR8","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/S0166-2236(02)02254-3","volume":"25","author":"GP Ahern","year":"2002","unstructured":"Ahern, G. P., Klyachko, V. A. & Jackson, M. B. cGMP and S-nitrosylation: two routes for modulation of neuronal excitability by NO. Trends in neurosciences \n                           25, 510\u2013517, doi:10.1016\/S0166-2236(02)02254-3 (2002).","journal-title":"Trends in neurosciences"},{"key":"2275_CR9","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/35055104","volume":"3","author":"SR Jaffrey","year":"2001","unstructured":"Jaffrey, S. R., Erdjument-Bromage, H., Ferris, C. D., Tempst, P. & Snyder, S. H. Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nature cell biology \n                           3, 193\u2013197, doi:10.1038\/35055104 (2001).","journal-title":"Nature cell biology"},{"key":"2275_CR10","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/nrm1569","volume":"6","author":"DT Hess","year":"2005","unstructured":"Hess, D. T., Matsumoto, A., Kim, S. O., Marshall, H. E. & Stamler, J. S. Protein S-nitrosylation: purview and parameters. Nature reviews. Molecular cell biology \n                           6, 150\u2013166, doi:10.1038\/nrm1569 (2005).","journal-title":"Nature reviews. Molecular cell biology"},{"key":"2275_CR11","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/S0896-6273(00)80310-4","volume":"18","author":"JS Stamler","year":"1997","unstructured":"Stamler, J. S., Toone, E. J., Lipton, S. A. & Sucher, N. J. (S)NO signals: translocation, regulation, and a consensus motif. Neuron \n                           18, 691\u2013696, doi:10.1016\/S0896-6273(00)80310-4 (1997).","journal-title":"Neuron"},{"key":"2275_CR12","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/S0166-2236(00)01929-9","volume":"24","author":"A Zagon","year":"2001","unstructured":"Zagon, A. Does the vagus nerve mediate the sixth sense? Trends in neurosciences \n                           24, 671\u2013673, doi:10.1016\/S0166-2236(00)01929-9 (2001).","journal-title":"Trends in neurosciences"},{"key":"2275_CR13","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1038\/nature01321","volume":"420","author":"KJ Tracey","year":"2002","unstructured":"Tracey, K. J. The inflammatory reflex. Nature \n                           420, 853\u2013859, doi:10.1038\/nature01321 (2002).","journal-title":"Nature"},{"key":"2275_CR14","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1038\/nri2566","volume":"9","author":"KJ Tracey","year":"2009","unstructured":"Tracey, K. J. Reflex control of immunity. Nature reviews. Immunology \n                           9, 418\u2013428, doi:10.1038\/nri2566 (2009).","journal-title":"Nature reviews. Immunology"},{"key":"2275_CR15","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/j.coph.2003.06.011","volume":"3","author":"KN Browning","year":"2003","unstructured":"Browning, K. N. Excitability of nodose ganglion cells and their role in vago-vagal reflex control of gastrointestinal function. Current opinion in pharmacology \n                           3, 613\u2013617, doi:10.1016\/j.coph.2003.06.011 (2003).","journal-title":"Current opinion in pharmacology"},{"key":"2275_CR16","doi-asserted-by":"publisher","first-page":"638","DOI":"10.3109\/00365529309096103","volume":"28","author":"S Lindgren","year":"1993","unstructured":"Lindgren, S., Stewenius, J., Sjolund, K., Lilja, B. & Sundkvist, G. Autonomic vagal nerve dysfunction in patients with ulcerative colitis. Scandinavian journal of gastroenterology \n                           28, 638\u2013642, doi:10.3109\/00365529309096103 (1993).","journal-title":"Scandinavian journal of gastroenterology"},{"key":"2275_CR17","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1136\/gutjnl-2013-304676","volume":"63","author":"G Matteoli","year":"2014","unstructured":"Matteoli, G. et al. A distinct vagal anti-inflammatory pathway modulates intestinal muscularis resident macrophages independent of the spleen. Gut \n                           63, 938\u2013948, doi:10.1136\/gutjnl-2013-304676 (2014).","journal-title":"Gut"},{"key":"2275_CR18","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1097\/00001756-200507130-00018","volume":"16","author":"A Orr-Urtreger","year":"2005","unstructured":"Orr-Urtreger, A., Kedmi, M., Rosner, S., Karmeli, F. & Rachmilewitz, D. Increased severity of experimental colitis in alpha 5 nicotinic acetylcholine receptor subunit-deficient mice. Neuroreport \n                           16, 1123\u20131127, doi:10.1097\/00001756-200507130-00018 (2005).","journal-title":"Neuroreport"},{"key":"2275_CR19","doi-asserted-by":"publisher","first-page":"e69424","DOI":"10.1371\/journal.pone.0069424","volume":"8","author":"P Sun","year":"2013","unstructured":"Sun, P. et al. Involvement of MAPK\/NF-kappaB signaling in the activation of the cholinergic anti-inflammatory pathway in experimental colitis by chronic vagus nerve stimulation. PloS One \n                           8, e69424, doi:10.1371\/journal.pone.0069424 (2013).","journal-title":"PloS One"},{"key":"2275_CR20","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.lfs.2009.10.009","volume":"85","author":"H Uneyama","year":"2009","unstructured":"Uneyama, H., Niijima, A., Kitamura, A. & Torii, K. Existence of NO-triggered vagal afferent activation in the rat gastric mucosa. Life sciences \n                           85, 782\u2013787, doi:10.1016\/j.lfs.2009.10.009 (2009).","journal-title":"Life sciences"},{"key":"2275_CR21","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/j.1365-2982.2004.00585.x","volume":"17","author":"CY Liu","year":"2005","unstructured":"Liu, C. Y., Jiang, W., Muller, M. H., Grundy, D. & Kreis, M. E. Sensitization of mesenteric afferents to chemical and mechanical stimuli following systemic bacterial lipopolysaccharide. Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society \n                           17, 89\u2013101, doi:10.1111\/j.1365-2982.2004.00585.x (2005).","journal-title":"Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society"},{"key":"2275_CR22","doi-asserted-by":"publisher","first-page":"G1213","DOI":"10.1152\/ajpgi.00267.2006","volume":"292","author":"CY Liu","year":"2007","unstructured":"Liu, C. Y., Mueller, M. H., Grundy, D. & Kreis, M. E. Vagal modulation of intestinal afferent sensitivity to systemic LPS in the rat. American journal of physiology. Gastrointestinal and liver physiology \n                           292, G1213\u20131220, doi:10.1152\/ajpgi.00267.2006 (2007).","journal-title":"American journal of physiology. Gastrointestinal and liver physiology"},{"key":"2275_CR23","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1742-2094-9-30","volume":"9","author":"CM Xia","year":"2012","unstructured":"Xia, C. M. et al. Up-regulation of brain-derived neurotrophic factor in primary afferent pathway regulates colon-to-bladder cross-sensitization in rat. Journal of neuroinflammation \n                           9, 30, doi:10.1186\/1742-2094-9-30 (2012).","journal-title":"Journal of neuroinflammation"},{"key":"2275_CR24","doi-asserted-by":"publisher","first-page":"5741","DOI":"10.4049\/jimmunol.1102147","volume":"188","author":"ES Fernandes","year":"2012","unstructured":"Fernandes, E. S. et al. TRPV1 deletion enhances local inflammation and accelerates the onset of systemic inflammatory response syndrome. Journal of immunology \n                           188, 5741\u20135751, doi:10.4049\/jimmunol.1102147 (2012).","journal-title":"Journal of immunology"},{"key":"2275_CR25","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/nchembio821","volume":"2","author":"T Yoshida","year":"2006","unstructured":"Yoshida, T. et al. Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nature chemical biology \n                           2, 596\u2013607, doi:10.1038\/nchembio821 (2006).","journal-title":"Nature chemical biology"},{"issue":"Suppl 1","key":"2275_CR26","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1111\/j.1743-3150.2004.00471.x","volume":"16","author":"HR Berthoud","year":"2004","unstructured":"Berthoud, H. R., Blackshaw, L. A., Brookes, S. J. & Grundy, D. Neuroanatomy of extrinsic afferents supplying the gastrointestinal tract. Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society \n                           16(Suppl 1), 28\u201333, doi:10.1111\/j.1743-3150.2004.00471.x (2004).","journal-title":"Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society"},{"key":"2275_CR27","doi-asserted-by":"publisher","first-page":"G211","DOI":"10.1152\/ajpgi.00128.2012","volume":"304","author":"A Perez-Burgos","year":"2013","unstructured":"Perez-Burgos, A. et al. Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents. American journal of physiology. Gastrointestinal and liver physiology \n                           304, G211\u2013220, doi:10.1152\/ajpgi.00128.2012 (2013).","journal-title":"American journal of physiology. Gastrointestinal and liver physiology"},{"key":"2275_CR28","doi-asserted-by":"publisher","first-page":"211","DOI":"10.4196\/kjpp.2012.16.3.211","volume":"16","author":"Y Jin","year":"2012","unstructured":"Jin, Y., Kim, J. & Kwak, J. Activation of the cGMP\/Protein Kinase G Pathway by Nitric Oxide Can Decrease TRPV1 Activity in Cultured Rat Dorsal Root Ganglion Neurons. The Korean journal of physiology & pharmacology: official journal of the Korean Physiological Society and the Korean Society of Pharmacology \n                           16, 211\u2013217, doi:10.4196\/kjpp.2012.16.3.211 (2012).","journal-title":"The Korean journal of physiology & pharmacology: official journal of the Korean Physiological Society and the Korean Society of Pharmacology"},{"key":"2275_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000201214","volume":"56","author":"SK Konturek","year":"1995","unstructured":"Konturek, S. K. & Konturek, P. C. Role of nitric oxide in the digestive system. Digestion \n                           56, 1\u201313, doi:10.1159\/000201214 (1995).","journal-title":"Digestion"},{"key":"2275_CR30","first-page":"211","volume":"52","author":"A Szlachcic","year":"2001","unstructured":"Szlachcic, A., Bilski, R., Dziadus-Sokolowska, A., Michalski, J. & Mroczka, J. The effect of nitric oxide donors and L-arginine on the gastric electrolyte barrier. Journal of physiology and pharmacology: an official journal of the Polish Physiological Society \n                           52, 211\u2013220 (2001).","journal-title":"Journal of physiology and pharmacology: an official journal of the Polish Physiological Society"},{"key":"2275_CR31","first-page":"611","volume":"52","author":"PC Konturek","year":"2001","unstructured":"Konturek, P. C. et al. Central and peripheral neural aspects of gastroprotective and ulcer healing effects of lipopolysaccharides. Journal of physiology and pharmacology: an official journal of the Polish Physiological Society \n                           52, 611\u2013623 (2001).","journal-title":"Journal of physiology and pharmacology: an official journal of the Polish Physiological Society"},{"key":"2275_CR32","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1080\/00365520310007152","volume":"39","author":"F Lamine","year":"2004","unstructured":"Lamine, F. et al. Nitric oxide released by Lactobacillus farciminis improves TNBS-induced colitis in rats. Scandinavian journal of gastroenterology \n                           39, 37\u201345, doi:10.1080\/00365520310007152 (2004).","journal-title":"Scandinavian journal of gastroenterology"},{"key":"2275_CR33","doi-asserted-by":"publisher","first-page":"9099","DOI":"10.3390\/molecules20059099","volume":"20","author":"M Magierowski","year":"2015","unstructured":"Magierowski, M., Magierowska, K., Kwiecien, S. & Brzozowski, T. Gaseous mediators nitric oxide and hydrogen sulfide in the mechanism of gastrointestinal integrity, protection and ulcer healing. Molecules \n                           20, 9099\u20139123, doi:10.3390\/molecules20059099 (2015).","journal-title":"Molecules"},{"key":"2275_CR34","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1097\/00042737-200012010-00015","volume":"12","author":"FH Mourad","year":"2000","unstructured":"Mourad, F. H., Khuri, M., Shouaib, F. & Nassar, C. F. Protective effect of the nitric oxide donor molsidomine on indomethacin and aspirin-induced gastric injury in rats. European journal of gastroenterology & hepatology \n                           12, 81\u201384 (2000).","journal-title":"European journal of gastroenterology & hepatology"},{"key":"2275_CR35","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1111\/j.1600-065X.2012.01138.x","volume":"248","author":"PS Olofsson","year":"2012","unstructured":"Olofsson, P. S., Rosas-Ballina, M., Levine, Y. A. & Tracey, K. J. Rethinking inflammation: neural circuits in the regulation of immunity. Immunological reviews \n                           248, 188\u2013204, doi:10.1111\/j.1600-065X.2012.01138.x (2012).","journal-title":"Immunological reviews"},{"issue":"e193","key":"2275_CR36","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1111\/j.1365-2982.2011.01824.x","volume":"24","author":"C Cailotto","year":"2012","unstructured":"Cailotto, C. et al. Neuroanatomical evidence demonstrating the existence of the vagal anti-inflammatory reflex in the intestine. Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society \n                           24(e193), 191\u2013200, doi:10.1111\/j.1365-2982.2011.01824.x (2012).","journal-title":"Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society"},{"key":"2275_CR37","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/288373a0","volume":"288","author":"RF Furchgott","year":"1980","unstructured":"Furchgott, R. F. & Zawadzki, J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature \n                           288, 373\u2013376, doi:10.1038\/288373a0 (1980).","journal-title":"Nature"},{"key":"2275_CR38","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1111\/j.1748-1716.1992.tb09359.x","volume":"145","author":"S Moncada","year":"1992","unstructured":"Moncada, S. The 1991 Ulf von Euler Lecture. The L-arginine: nitric oxide pathway. Acta physiologica Scandinavica \n                           145, 201\u2013227, doi:10.1111\/j.1748-1716.1992.tb09359.x (1992).","journal-title":"Acta physiologica Scandinavica"},{"key":"2275_CR39","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1097\/00001756-200101220-00032","volume":"12","author":"DC Kelly","year":"2001","unstructured":"Kelly, D. C., Asghar, A. U., Marr, C. G. & McQueen, D. S. Nitric oxide modulates articular sensory discharge and responsiveness to bradykinin in normal and arthritic rats in vivo. Neuroreport \n                           12, 121\u2013125, doi:10.1097\/00001756-200101220-00032 (2001).","journal-title":"Neuroreport"},{"key":"2275_CR40","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1152\/jn.00058.2004","volume":"92","author":"D Levy","year":"2004","unstructured":"Levy, D. & Strassman, A. M. Modulation of dural nociceptor mechanosensitivity by the nitric oxide-cyclic GMP signaling cascade. Journal of neurophysiology \n                           92, 766\u2013772, doi:10.1152\/jn.00058.2004 (2004).","journal-title":"Journal of neurophysiology"},{"key":"2275_CR41","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1038\/sj.bjp.0705181","volume":"138","author":"GG Vivancos","year":"2003","unstructured":"Vivancos, G. G., Parada, C. A. & Ferreira, S. H. Opposite nociceptive effects of the arginine\/NO\/cGMP pathway stimulation in dermal and subcutaneous tissues. British journal of pharmacology \n                           138, 1351\u20131357, doi:10.1038\/sj.bjp.0705181 (2003).","journal-title":"British journal of pharmacology"},{"key":"2275_CR42","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S0304-3940(99)00553-4","volume":"271","author":"K Bielefeldt","year":"1999","unstructured":"Bielefeldt, K., Whiteis, C. A., Chapleau, M. W. & Abboud, F. M. Nitric oxide enhances slow inactivation of voltage-dependent sodium currents in rat nodose neurons. Neuroscience letters \n                           271, 159\u2013162, doi:10.1016\/S0304-3940(99)00553-4 (1999).","journal-title":"Neuroscience letters"},{"key":"2275_CR43","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/S0092-8674(01)00495-0","volume":"106","author":"JS Stamler","year":"2001","unstructured":"Stamler, J. S., Lamas, S. & Fang, F. C. Nitrosylation. the prototypic redox-based signaling mechanism. Cell \n                           106, 675\u2013683 (2001).","journal-title":"Cell"},{"key":"2275_CR44","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1038\/sj.cdd.4400580","volume":"6","author":"SA Lipton","year":"1999","unstructured":"Lipton, S. A. Neuronal protection and destruction by NO. Cell death and differentiation \n                           6, 943\u2013951, doi:10.1038\/sj.cdd.4400580 (1999).","journal-title":"Cell death and differentiation"},{"key":"2275_CR45","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1038\/39807","volume":"389","author":"MJ Caterina","year":"1997","unstructured":"Caterina, M. J. et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature \n                           389, 816\u2013824, doi:10.1038\/39807 (1997).","journal-title":"Nature"},{"key":"2275_CR46","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/S0896-6273(00)80564-4","volume":"21","author":"M Tominaga","year":"1998","unstructured":"Tominaga, M. et al. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron \n                           21, 531\u2013543, doi:10.1016\/S0896-6273(00)80564-4 (1998).","journal-title":"Neuron"},{"key":"2275_CR47","doi-asserted-by":"publisher","first-page":"130","DOI":"10.2174\/138920111793937844","volume":"12","author":"JP White","year":"2011","unstructured":"White, J. P., Urban, L. & Nagy, I. TRPV1 function in health and disease. Current pharmaceutical biotechnology \n                           12, 130\u2013144, doi:10.2174\/138920111793937844 (2011).","journal-title":"Current pharmaceutical biotechnology"},{"key":"2275_CR48","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1126\/science.288.5464.306","volume":"288","author":"MJ Caterina","year":"2000","unstructured":"Caterina, M. J. et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science \n                           288, 306\u2013313, doi:10.1126\/science.288.5464.306 (2000).","journal-title":"Science"},{"key":"2275_CR49","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/35012076","volume":"405","author":"JB Davis","year":"2000","unstructured":"Davis, J. B. et al. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature \n                           405, 183\u2013187, doi:10.1038\/35012076 (2000).","journal-title":"Nature"},{"key":"2275_CR50","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s00424-005-1457-8","volume":"451","author":"M Tominaga","year":"2005","unstructured":"Tominaga, M. & Tominaga, T. Structure and function of TRPV1. Pflugers Archiv: European journal of physiology \n                           451, 143\u2013150, doi:10.1007\/s00424-005-1457-8 (2005).","journal-title":"Pflugers Archiv: European journal of physiology"},{"key":"2275_CR51","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.ejphar.2013.05.009","volume":"715","author":"L Pan","year":"2013","unstructured":"Pan, L., Song, K., Hu, F., Sun, W. & Lee, I. Nitric oxide induces apoptosis associated with TRPV1 channel-mediated Ca(2+) entry via S-nitrosylation in osteoblasts. European journal of pharmacology \n                           715, 280\u2013285, doi:10.1016\/j.ejphar.2013.05.009 (2013).","journal-title":"European journal of pharmacology"},{"key":"2275_CR52","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jneumeth.2007.04.003","volume":"164","author":"BY Li","year":"2007","unstructured":"Li, B. Y. & Schild, J. H. Electrophysiological and pharmacological validation of vagal afferent fiber type of neurons enzymatically isolated from rat nodose ganglia. Journal of neuroscience methods \n                           164, 75\u201385, doi:10.1016\/j.jneumeth.2007.04.003 (2007).","journal-title":"Journal of neuroscience methods"},{"key":"2275_CR53","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/S0306-4522(99)00547-3","volume":"96","author":"LA Blackshaw","year":"2000","unstructured":"Blackshaw, L. A., Page, A. J. & Partosoedarso, E. R. Acute effects of capsaicin on gastrointestinal vagal afferents. Neuroscience \n                           96, 407\u2013416, doi:10.1016\/S0306-4522(99)00547-3 (2000).","journal-title":"Neuroscience"},{"key":"2275_CR54","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1007\/BF02065548","volume":"40","author":"T Watanabe","year":"1995","unstructured":"Watanabe, T., Arakawa, T., Fukuda, T., Higuchi, K. & Kobayashi, K. Zinc deficiency delays gastric ulcer healing in rats. Digestive diseases and sciences \n                           40, 1340\u20131344, doi:10.1007\/BF02065548 (1995).","journal-title":"Digestive diseases and sciences"},{"key":"2275_CR55","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/S0304-3940(98)00690-9","volume":"255","author":"K Hillsley","year":"1998","unstructured":"Hillsley, K. & Grundy, D. Serotonin and cholecystokinin activate different populations of rat mesenteric vagal afferents. Neuroscience letters \n                           255, 63\u201366, doi:10.1016\/S0304-3940(98)00690-9 (1998).","journal-title":"Neuroscience letters"},{"issue":"Pt 2","key":"2275_CR56","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1113\/jphysiol.1996.sp021781","volume":"497","author":"W Richards","year":"1996","unstructured":"Richards, W., Hillsley, K., Eastwood, C. & Grundy, D. Sensitivity of vagal mucosal afferents to cholecystokinin and its role in afferent signal transduction in the rat. The Journal of physiology \n                           497(Pt 2), 473\u2013481, doi:10.1113\/jphysiol.1996.sp021781 (1996).","journal-title":"The Journal of physiology"},{"key":"2275_CR57","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/nmo.12469","volume":"27","author":"J Li","year":"2015","unstructured":"Li, J. et al. Oxytocin down-regulates mesenteric afferent sensitivity via the enteric OTR\/nNOS\/NO\/KATP pathway in rat. Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society \n                           27, 51\u201362, doi:10.1111\/nmo.12469 (2015).","journal-title":"Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society"},{"issue":"Pt 2","key":"2275_CR58","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1111\/j.1469-7793.1998.551bw.x","volume":"506","author":"K Hillsley","year":"1998","unstructured":"Hillsley, K., Kirkup, A. J. & Grundy, D. Direct and indirect actions of 5-hydroxytryptamine on the discharge of mesenteric afferent fibres innervating the rat jejunum. The Journal of physiology \n                           506(Pt 2), 551\u2013561, doi:10.1111\/tjp.1998.506.issue-2 (1998).","journal-title":"The Journal of physiology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02275-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02275-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02275-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T04:23:35Z","timestamp":1671769415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02275-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,18]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["2275"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-02275-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,18]]},"assertion":[{"value":"20 December 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"2063"}}