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https://hdl.handle.net/2440/89964
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Type: | Journal article |
Title: | Diet-dependent modulation of gastro-oesphageal vagal afferent mechanosensitivity by endogenous nitric oxide |
Author: | Kentish, S. O'Donnell, T. Wittert, G. Page, A. |
Citation: | The Journal of Physiology, 2014; 592(15):3287-3301 |
Publisher: | Wiley-Blackwell Publishing |
Issue Date: | 2014 |
ISSN: | 0022-3751 1469-7793 |
Statement of Responsibility: | Stephen J. Kentish, Tracey A. O'Donnell, Gary A. Wittert and Amanda J. Page |
Abstract: | Neuronal nitric oxide (NO) plays an important role in gastric motor activity and modulates the mechanosensitivity of gastro-oesophageal vagal afferents. Effects of NO on food intake are dependent on feeding status. We sought to determine the effect of NO on gastro-oesophageal vagal afferent activity in the normally fed and food-restricted states and the second messenger pathways mediating these effects. Eight week old female C56BL/6 mice were fed ad libitum or food restricted for 14 h. An in vitro 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-transcription polymerase chain reaction (RT-PCR). Endogenous NO and the NO donor S-nitroso-N-acetylpenicillamine (SNAP) inhibited vagal mucosal afferent responses to tactile stimuli in mice fed ad libitum. After a 14 h 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 h fast expression of NADPH oxidase 2 (NOX2) mRNA in whole nodose ganglia was significantly reduced and the excitatory effect of NO on gastro-oesophageal vagal afferents was lost. Under fasting conditions the inhibitory effect of NO was blocked with the hyperpolarisation-activated cyclic nucleotide-gated (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-oesophageal vagal afferents is dynamic and dependent on feeding status. |
Keywords: | Esophagus Nodose Ganglion Neurons, Afferent Animals Mice, Inbred C57BL Mice Nitric Oxide Acetophenones Benzazepines Potassium Channels Membrane Glycoproteins Diet Mechanotransduction, Cellular Female Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels NADPH Oxidase 2 NADPH Oxidases Ivabradine |
Rights: | © 2014 The Authors. The Journal of Physiology © 2014 The physiological Society |
DOI: | 10.1113/jphysiol.2014.272674 |
Published version: | http://dx.doi.org/10.1113/jphysiol.2014.272674 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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