Sensory Signal Transduction in the Vagal Primary Afferent Neurons

Abstract

The vagal nerve conveys primary afferent information from the intestinal mucosa to the brain stem. Activation of vagal afferent fibers results in inhibition of food intake, gastric emptying, and stimulation of pancreatic secretion. Afferents nerves terminating near to the mucosa are in a position to monitor the composition of the luminal contents. As afferents do not project directly into the lumen, their activation depends on an intermediary step, i.e. neuronal activation by a secondary substance released from within the mucosal epithelium. This review addresses the role for both cholecytokinin (CCK) and serotonin (5-HT) released from enteroendocrine cells and acting as paracrine agents on the terminals of vagal afferents in responses to a number of luminal signals. CCK acted on both high- and low-affinity CCK-A receptors present on distinct vagal primary afferent neurons. Neurons of the nodose ganglia respond to intraduodenal perfusions of maltose, glucose, and hypertonic saline. These neurons were also sensitive to exogenous luminally applied 5-HT at concentrations that mimic physiologic levels. Intravenous administration of a 5-HT3 antagonist blocked these responses suggesting that nodose neuronal responses to luminal osmolarity and to the digestion products of carbohydrates are dependent on the release of endogenous 5-HT from the mucosal enterochromaffin (EC) cells, which acts on the 5-HT3 receptors on vagal afferent fibers to stimulate vagal afferent neurons. Double-labeling studies revealed that nodose neurons responded to 5-HT-dependent luminal stimuli contain mainly glutamate and substance P. Over the past year or so it has become clear that there are multiple possible excitatory inputs to a common vagal afferent route with synergistic interactions being common. The nodose ganglion contains neurons that may possess only high- or low-affinity CCK-A receptors or 5-HT3 receptors. Some neurons that express high-affinity CCK-A receptors also express 5-HT3 receptors and (or) secretin receptors. Pre-exposure to luminal 5-HT may augment the subsequent response to a subthreshold dose of CCK. Synergistic interaction between CCK and secretin also occurs at the nodose ganglia; this is mediated by high affinity CCK-A receptor. This may explain the robust postprandial secretion of enzyme, bicarbonate, and fluid despite the modest increase in CCK after a meal. Some neurons that possess low-affinity CCK-A receptor colocalize with leptin receptors (OB-Rs). These neurons also respond to mechanical distention. Interaction between CCK-A receptor and OB-Rs in these neurons likely facilitates leptin mediation of short-term satiety.

Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system

“…Peptone can also induce the activities of the peptidergic and cholinergic neurons in the gastrointestinal tract (48). Through LPA5, FPP increases nerve activities in cultured DRG neurons, as indicated by the elevation of [Ca 2ϩ ] i (59).…”

Subdiaphragmatic vagal afferent nerves modulate visceral pain

“…By using electrophysiological recording of vagal afferent neurons in nodose ganglia, we have shown previously that electrical stimulation of subdiaphragmatic vagal afferent fibers enhanced the conduction of afferent signals (30). The ability to depolarize nerve fibers by means of electrical stimulation depends on the intensity and duration (e.g., magnitude of the current and the width of the pulse) of the stimulus.…”

“…Body temperature was maintained with a special heating pad. The right nodose ganglion was exposed by a short dorsal approach as previously described (30,57). The beveled glass recording micropipette filled with 1.0 M KCl was lowered into the nodose ganglion.…”

Gastric leptin: a novel role in cardiovascular regulation

“…Relative to adiposederived leptin, the gastric pool of leptin is small and unlikely to significantly alter circulating levels (1), suggesting that its actions may be confined to the gut. This source of leptin is mobilized in response to food intake and may act in a paracrine fashion on subdiaphragmatic vagal afferents, different to the mode of action for adipose leptin (1,4,19,25). Leptin applied within the gut acutely activates a subpopulation of neurons in the nucleus of the solitary tract that are also responsive to gastric vagal stimulation (42).…”

“…Adipose leptin is actively and unidirectionally transported into the central nervous system and is thought to regulate appetite, thermogenesis, and sympathetic outflow by inducing transcriptional changes in the hypothalamus (16,22). On the other hand, many of the effects of gastric leptin have, to date, been shown to be acute and dependent on vagal afferent transmission (1,4,19,25). To identify a difference between the cardiovascular effects of gastric versus adipose sources of leptin, a comparison of the effects of intravenous (mimicking adipose-derived leptin that is released into the general circulation) versus close arterial leptin administration was also made.…”