{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T06:47:12Z","timestamp":1771051632704,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2014,6,19]],"date-time":"2014-06-19T00:00:00Z","timestamp":1403136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Health and Medical Research Council of Australia (NHMRC)","award":["565186"],"award-info":[{"award-number":["565186"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Nitric oxide (NO) is an important signalling molecule found in the gastrointestinal tract, which can modulate the mechanosensitivity of gastro\u2010oesophageal vagal afferents.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>It is known that the effects of NO on food intake depend on feeding status, but the effect of NO on gastro\u2010oesophageal vagal afferents in different feeding conditions is unknown.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>We show that in the fed state endogenous NO inhibits mucosal afferents through a pathway involving nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In mice fasted overnight endogenous NO potentiates the response of mucosal stroking\u2010 and tension\u2010sensitive afferents to mechanical stimuli via a mechanism involving hyperpolarisation\u2010activated cyclic nucleotide\u2010gated 3 (HCN3) channels.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>These results show the role of NO in the peripheral modulation of gastro\u2010oesophageal vagal afferents is dynamic and dependent on feeding status.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Neuronal nitric oxide (NO) plays an important role in gastric motor activity and modulates the mechanosensitivity of gastro\u2010oesophageal vagal afferents. Effects of NO on food intake are dependent on feeding status. We sought to determine the effect of NO on gastro\u2010oesophageal vagal afferent activity in the normally fed and food\u2010restricted states and the second messenger pathways mediating these effects. Eight week old female C56BL\/6 mice were fed<jats:italic>ad libitum<\/jats:italic>or food restricted for 14\u00a0h. An<jats:italic>in vitro<\/jats:italic>preparation was used to determine the functional effects of NO and the second messenger pathways involved. Expression of NO signal transduction molecules in vagal afferents was determined by reverse\u2010transcription polymerase chain reaction (RT\u2010PCR). Endogenous NO and the NO donor<jats:italic>S<\/jats:italic>\u2010nitroso\u2010<jats:italic>N<\/jats:italic>\u2010acetylpenicillamine (SNAP) inhibited vagal mucosal afferent responses to tactile stimuli in mice fed<jats:italic>ad libitum<\/jats:italic>. After a 14\u00a0h fast endogenous NO and SNAP potentiated tension and mucosal afferent responses to mechanical stimulation. The excitatory effect of NO was blocked by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin. After a 14\u00a0h fast expression of NADPH oxidase 2 (NOX2) mRNA in whole nodose ganglia was significantly reduced and the excitatory effect of NO on gastro\u2010oesophageal vagal afferents was lost. Under fasting conditions the inhibitory effect of NO was blocked with the hyperpolarisation\u2010activated cyclic nucleotide\u2010gated (HCN) channel blocker ivabradine and mRNA expression of HCN3 in the nodose ganglia was elevated. In conclusion, the role of NO in the peripheral modulation of gastro\u2010oesophageal vagal afferents is dynamic and dependent on feeding status.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.272674","type":"journal-article","created":{"date-parts":[[2014,5,31]],"date-time":"2014-05-31T04:03:42Z","timestamp":1401509022000},"page":"3287-3301","source":"Crossref","is-referenced-by-count":14,"title":["Diet\u2010dependent modulation of gastro\u2010oesphageal vagal afferent mechanosensitivity by endogenous nitric oxide"],"prefix":"10.1113","volume":"592","author":[{"given":"Stephen J.","family":"Kentish","sequence":"first","affiliation":[{"name":"Nerve\u2010Gut Research Laboratory Department of Medicine University of Adelaide Adelaide Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracey A.","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Nerve\u2010Gut Research Laboratory Department of Medicine University of Adelaide Adelaide 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