Premium
Diet‐dependent modulation of gastro‐oesphageal vagal afferent mechanosensitivity by endogenous nitric oxide
Author(s) -
Kentish Stephen J.,
O'Donnell Tracey A.,
Wittert Gary A.,
Page Amanda J.
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.272674
Subject(s) - endogeny , nitric oxide , vagus nerve , nicotinamide adenine dinucleotide phosphate , medicine , endocrinology , chemistry , biology , biochemistry , stimulation , enzyme , oxidase test
Key points Nitric oxide (NO) is an important signalling molecule found in the gastrointestinal tract, which can modulate the mechanosensitivity of gastro‐oesophageal vagal afferents. It is known that the effects of NO on food intake depend on feeding status, but the effect of NO on gastro‐oesophageal vagal afferents in different feeding conditions is unknown. We show that in the fed state endogenous NO inhibits mucosal afferents through a pathway involving nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In mice fasted overnight endogenous NO potentiates the response of mucosal stroking‐ and tension‐sensitive afferents to mechanical stimuli via a mechanism involving hyperpolarisation‐activated cyclic nucleotide‐gated 3 (HCN3) channels. These results show the role of NO in the peripheral modulation of gastro‐oesophageal vagal afferents is dynamic and dependent on feeding status.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.