Tomio Shingai

Sour taste stimulation facilitates reflex swallowing from the pharynx and larynx in the rat

Chemical stimulation of the pharynx and larynx is effective in eliciting reflex swallowing. A sour taste bolus facilitates the onset of swallowing in patients with neurogenic dysphagia, but the mechanism of the facilitation has not been clarified. We investigated the effect of sour solutions on the elicitation of reflex swallowing in anesthetized rats. The main ducts of salivary glands were ligated to avoid the effect of saliva. A small amount of water, sour solutions, and other taste solutions were applied to the mucosa of the pharyngolaryngeal region. Acetic acid and citric acid, which provide a sour taste, had a stronger effect on evoking reflex swallowing as compared with other taste solutions. The effectiveness of these acids increased with increasing concentrations. We also examined the contribution of the superior laryngeal nerve (SLN) and the pharyngeal branch of the glossopharyngeal nerve (GPNph) to reflex swallowing. Acetic acid was greatly effective in evoking swallowing in both the region innervated by the SLN and the GPNph. On the other hand, water was effective in the SLN region but only slightly effective in the GPNph region. The results indicate that stimulation of the pharyngolaryngeal region with sour solutions facilitates reflex swallowing, suggesting that the facilitation may be due to increases of sensory inputs via the SLN and GPNph.

Role of the pharyngeal branch of the vagus nerve in laryngeal elevation and UES pressure during swallowing in rabbits.

Elevation of the larynx during swallowing plays an important role in protecting the laryngeal inlet and in the opening of the upper esophageal sphincter (UES). The thyrohyoid (TH) muscle is the most important muscle for laryngeal elevation, and it is thought to be innervated by the thyrohyoid branch. However, in preliminary studies we found that laryngeal elevation was severely disturbed after sectioning of the pharyngeal branch of the vagus nerve (X-ph). In the present study, we examined the role of the X-ph in laryngeal elevation and the contribution of this nerve to UES pressure. Ten male rabbits under anesthesia were used. Sectioning of the X-ph not only abolished the electromyographic activities of the TH and cricopharyngeus (CP) muscles, it also greatly reduced the maximal value of laryngeal elevation during swallowing. On the other hand, sectioning of the hypoglossal nerve, which contains the thyrohyoid branch, produced no appreciable change in the electromyographic activity of either muscle and it reduced the maximal value of the elevation only slightly. These results indicate that the X-ph innervates the TH and CP muscles and suggest that the X-ph plays an important role in elevating the larynx and in regulating the UES pressure in rabbits.

Diuresis mediated by the superior laryngeal nerve in rats

Diuresis mediated by the superior laryngeal nerve (SLN) was investigated using pentobarbital-anesthetized rats. A marked increase in urine flow was induced by application of water to the larynx. The diuretic effect of water was conspicuous during the first 30 min after the application and lasted for more than 1 hr. In contrast, a 160 mM solution of NaCl produced only slight diuresis. After bilateral sectioning of the SLNs, water-induced diuresis was considerably reduced. The results suggest that water fibers contained in the SLN may make a major contribution to the diuresis.

Responses of Neurons in the Parabrachial Region of the Rat to Electrical Stimulation of the Superior Laryngeal Nerve and Chemical Stimulation of the Larynx

The responsiveness of the parabrachial region to electrical stimulation of the superior laryngeal nerve was first examined in anesthetized rats. Action potentials were recorded in 30 parabrachial sites by single and train electrical pulses to the superior laryngeal nerve. The average latency, from the onset of stimulation to the first action potentials, was 9.9 ms (range, 6.5-18.8 ms). The responsiveness of parabrachial neurons to chemical stimulation of the laryngeal region was next examined using anesthetized, immobilized, and artificially ventilated rats in which the chorda tympani and glossopharyngeal nerves were bilaterally sectioned. Taste stimuli were applied to the laryngeal region through a tracheal tube and rinsed with 0.15 NaCl. A total of 66 responses were recorded from 26 neurons. The most effective stimulus for these neurons was 0.03 M hydrochloric acid, followed by 0.01 M quinine hydrochloride, 0.5 M sodium chloride, 0.5 M sucrose, and distilled water. Seven responses were derived from 0.15 NaCl. These neurons were mainly located in a posterodorsolateral part of the parabrachial nucleus. These results suggest that chemical signals from the laryngeal region are transmitted to the parabrachial nucleus through the superior laryngeal nerve.

A comparison of voluntary salt-intake behavior in Nax-gene deficient and wild-type mice with reference to peripheral taste inputs

The Na(x) channel, a subfamily of voltage-gated sodium channels, is thought to be a specific sodium receptor in the central nervous system. Our previous study revealed that Na(x)-gene-deficient mice consumed excessive amounts of NaCl even under water-deprived conditions. In the present study, to investigate whether the peripheral taste inputs are involved in the abnormal intake of salt in Na(x)-deficient mice (homo), voluntary intake of various taste solutions in homo and wild-type mice (wild) was examined under non-deprived conditions. Homo showed a higher preference for 0.15 M NaCl solution than wild. Preference ratios for other basic tastants were identical between groups. Transection of the chorda tympani (CT) or the glossopharyngeal (GP) nerve had little effect on salt-intake behavior in homo and wild. Although combined transection of the superior laryngeal (SL) and GP nerves decreased NaCl intake in homo but not in wild, there were no differences in preference ratios for NaCl in homo before and after SL+GP transection. On the other hand, preference ratios for NaCl in wild tended to increase after combined SL and GP transection. Consequently, preference ratios for NaCl after SL+GP transection were no different between homo and wild. While electrophysiological responses of the CT and the GP to various taste solutions were indistinguishable between homo and wild, those of the SL to NaCl in homo were smaller than those in wild only at lower concentrations (0.01 and 0.03 M). Thus, chemosensory inputs from the oro-pharyngeal regions had little effect on abnormal salt intake in homo, if any. From these results, it is suggested that the higher preference for NaCl in homo is mainly due to the lack of Na(x) channels in the central nervous system.

Response properties of the pharyngeal branch of the glossopharyngeal nerve for umami taste in mice and rats

Many studies have reported the mechanism underlying umami taste. However, there are no investigations of responses to umami stimuli taste originating from chemoreceptors in the pharyngeal region. The pharyngeal branch of the glossopharyngeal nerve (GPN-ph) innervating the pharynx has unique responses to taste stimulation that differs from responses of the chorda tympani nerve and lingual branch of the glossopharyngeal nerve. Water evokes robust response, but NaCl solutions at physiological concentrations do not elicit responses. The present study was designed to examine umami taste (chemosensory) responses in the GPN-ph. Response characteristics to umami taste were compared between mice and rats. In mice, stimulation with compounds eliciting umami taste (0.1M monosodium L-glutamate (MSG), 0.01M inosine monophosphate (IMP) and the mixture of 0.1M MSG+0.01M IMP) evoked higher responses than application of distilled water (DW). However, synergistic response of a mixture of 0.1M MSG+0.01M IMP was not observed. In rats, there is no significant difference between the responses to umami taste (0.1M MSG, 0.01M IMP and the mixture of 0.1M MSG+0.01M IMP) and DW. Monopotassium glutamate (MPG) was used in rats to examine the contribution of the sodium component of MSG on the response. Stimulation with 0.1M MPG evoked a higher response when compared with responses to DW. The present results suggest that umami taste compounds are effective stimuli of the chemoreceptors in the pharynx of both mice and rats.

Changes in water intake following pharyngolaryngeal deafferentation in the rat

The role of afferent information arising from the pharyngolaryngeal region in the regulation of water intake was evaluated in rats. The animals received picric application to the mucosa of either the pharyngolaryngeal or the hard palate region. Water intake of the pharyngolaryngeal treated animals was reduced significantly, while no reduction in water intake was shown in the control and hard palate treated animals.

Responses of parabrachial nucleus neurons to chemical stimulation of posterior tongue in chorda tympani-sectioned rats

Responses of parabrachial nucleus (PBN) neurons (n = 43) to chemical stimulation of the posterior tongue were recorded in chorda tympani (CT)-sectioned rats and compared with those (n = 45) in CT-intact. The chemical stimuli used were 0.5 M sucrose, 0.5 M sodium chloride (NaCl), 0.03 M hydrochloric acid (HCl), 0.01 M quinine hydrochloride, and distilled water. These stimuli were applied to an area posterior to the intermolar eminence of the tongue. Neurons of CT-sectioned rats responsive to the chemical stimuli were located in more caudal areas of the PBN compared with those of CT-intact. Numbers of responses to the five stimuli and breadth of responsiveness to the four basics were not different between both groups of rats. However, average response magnitudes of the neurons in CT-sectioned rats were lower than those in CT-intact. In both groups of rats, the response magnitudes to NaCl and HCl were larger than those to the other three stimuli, and responses to NaCl and those to HCl were highly correlated. It is suggested that glossopharyngeal fibers responding strongly to acids and salts are likely to be the main source of PBN responses from the posterior tongue.

Hypotonic diuresis following oropharyngeal stimulation with water in humans

The role of oropharyngeal mechanisms in body water regulation was studied in 12 human males by measuring urine output and osmolality before and after drinking a very small volume of distilled water (0.15 ml/kg b.w.t.). Hypotonic diuresis was resulted only in the subjects (n = 6) who drank only sufficient water to keep their oropharynx moist continually over a 20 min period but not in those who (n = 6) drank the same volume of water within several seconds. Sham verbal instructions on drinking induced no changes in subjects examined. These results suggest that oropharyngeal afferents alone, and neither gastric afferents nor psychosomatic effects, may account for hypotonic diuresis following water intake in man.

Leptin modulates the response to oleic acid in the pharynx

Leptin released from the adipose tissues is known to inhibit obesity by regulating food intake. In this study, we investigated the effect of leptin on afferent nerve responses to fats and fatty acid in the pharyngolaryngeal region. The afferent nerve activities were recorded from the whole nerve bundle or pauci-fiber bundles of the pharyngeal branch of the glossopharyngeal nerve (GPN-ph) in Wistar normal and fatty rats. Oleic acid (long-chain fatty acid), mineral oil (nonfat oil) and safflower oil (vegetable oil; middle-chain fatty acid) were applied to the surface of pharyngolaryngeal mucous membrane. Oleic acid elicited vigorous stimulation of the GPN-ph activity in both normal and fatty rats but other oils had no significant effect on the activity. After intravenous administration of leptin (30 ng/kg, 1 ml), the response to oleic acid was significantly decreased in normal rats, whereas such a decrease was not found in fatty rats. These results are the first findings to indicate the existence of a suppressive mechanism of leptin on the response of the GPN-ph to fatty acid in normal rats, but that such a mechanism is lacking in fatty rats.