Oropharyngeal Receptors Research Articles

Popular Beverages Stimulate Oropharyngeal and Gut Receptors Eliciting Modulation of the Upper Digestive Processes

This paper reports clinical studies on the effect of agonists of taste and chemethesis receptors in the oropharyngeal cavity and the gut. The peripheral nerve system plays a vital role in our selection or rejection of what we eat and drink. Although the degree to which it is hard-wired has not been determined, it is known that our food and drink choices change with age. Scientific studies on the impact of food and drink on the body have been concerned predominantly with nutritional factors and, more recently, impacts on cholesterol and blood sugar levels. On the other hand, the sensations we experience during eating and drinking have long been regarded, perhaps even dismissed, as purely hedonistic. The idea that foods and drinks may actually influence digestion is a novel one and is based on the discovery 20 years ago of taste buds, innervated by the vagi, in stomach and intestinal tissues. Studies indicate some of our most popular drinks modulate both postprandial hyperaemia and gastric emptying. It is proposed that the bitter taste experienced with some foods and drinks promotes increased blood flow to the splanchnic circulation and slows the flow of chyme to the small intestine. In cases of toxicity, these actions promote emesis whereas at non-toxic levels, bitter substances promote digestion by increasing postprandial hyperaemia and slowing gastric emptying. Additionally, chemethesis agonists can act on the oropharyngeal receptors resulting in a slower gastric emptying. These effects may lead to a learned behaviour and subsequent enjoyment of bitter tastants, rather than their rejection, amongst those with reduced digestive capacity. It provides a rationale for the popularity of certain bitter tasting aperitifs and digestive alcoholic beverages originating in southern Europe.

Цетилпиридиния хлорид в составе комбинированных препаратов для взрослых и детей в период пандемии COVID-19: подтвержденные возможности и перспективы

Despite the measures taken, SARS-CoV-2 continues to spread. However, an increase in acute respiratory infections (ARIs) in autumn 2021 is accounted for by the circulation of seasonal respiratory viruses, i.e., rhinovirus, respiratory syncytial virus, adenovirus, etc. The development of novel agents and study of the antiviral activity of well-established agents that inhibit the binding of SARS-CoV-2 and other respiratory viruses with nasopharyngeal and oropharyngeal receptors significantly reduces viral load. Cetylpyridinium chloride is an antiseptic without searing or damaging oropharyngeal epithelium that provides local effects without systemic immunomodulatory action. This agent is approved in Russian Federation for topical use in children over three years and adults as a part of a combined medication for infectious inflammatory throat diseases. This paper reviews current published data illustrating the antiviral activity of cetylpyridinium and its potential application as an antiseptic for preventive and therapeutic use in the COVID-19 pandemic. KEYWORDS: cetylpyridinium chloride, SARS-CoV-2, antiseptic, coronavirus infection, COVID-19, direct antiviral effect. FOR CITATION: Melekhina E.V., Muzyka A.D., Ponezheva Zh.B., Gorelov A.V. Cetylpyridinium chloride as a part of a combined medication for adults and children during the COVID-19 pandemic: established and perspective use. Russian Medical Inquiry. 2021;5(11):728–736 (in Russ.). DOI: 10.32364/2587-6821-2021-5-11-728-736.

Carbohydrate Mouth Rinse Effects on Exercise Capacity in Pre- and Postprandial States

Background. Oropharyngeal receptors signal presence of carbohydrate to the brain. Mouth rinses with a carbohydrate solution facilitate corticomotor output and improve time-trial performance in well-trained subjects in a fasted state. We tested for this effect in nonathletic subjects in fasted and nonfasted state. Methods. 13 healthy non-athletic males performed 5 tests on a cycle ergometer. After measuring maximum power output (Wmax), the subjects cycled four times at 60% Wmax until exhaustion while rinsing their mouth every 5 minutes with either a 6.4% maltodextrin solution or water, one time after an overnight fast and another after a carbohydrate rich breakfast. Results. Mouth rinsing with maltodextrin improved time-to-exhaustion in pre- and postprandial states. This was accompanied by reductions in the average and maximal rates of perceived exertion but no change in average or maximal heart rate was observed. Conclusions. Carbohydrate mouth rinsing improves endurance capacity in both fed and fasted states in non-athletic subjects.

Visceral Nerves: Vagal and Sympathetic Innervation

The autonomic nervous system is the primary neural mediator of physiological responses to internal and external stimuli. It is composed of 2 branches: the sympathetic nervous system, which mediates catabolic responses, and the parasympathetic nervous system, composed of the vagus nerve, which regulates anabolic responses. As the vagus nerve innervates most tissues involved in nutrient metabolism, including the stomach, pancreas, and liver, activation of vagal efferent activity has the potential to influence how nutrients are absorbed and metabolized. Vagal efferent activity is initially activated at the onset of food intake by receptors in the oropharyngeal cavity and then during food intake postprandially. Vagal efferent innervation of the pancreas contributes to early-phase insulin release as well as to optimizing postprandial insulin release. In the absence of vagal activation, which occurs when glucose is administered intragastrically, postprandial glucose levels are higher and insulin levels blunted compared with when there is activation of oropharyngeal receptors by food. An induction of vagal efferent activity also occurs during chronic pancreatic B-cell challenge with 48-hour glucose infusions. Under these conditions, the compensatory increase in insulin secretion is partially mediated by an increase in vagal efferent activity. In conclusion, the vagus nerve, part of the parasympathetic nervous system, plays a critical role in the regulation of blood glucose levels and is an often overlooked factor contributing to glucose homeostasis.

Entero-pancreatic neurons are responsible for the intestinal phase of pre absorptive insulin secretion

Abstract Insulin is a key hormone of the intermediary metabolism and its early secretion after a meal has a major role in the overall organism glucose sensitivity. Pre absorptive insulin secretion (PAIS) includes a cephalic phase (implicating oro-pharyngeal receptors) and an intestinal phase (implicating gastric and duodenal receptors). Entero-pancreatic (EP) neurons, which originate from the antral and the proximal duodenal intrinsic nervous systems, form varicosities in pancreatic ganglia and islets and may account for the intestinal phase of PAIS. To test this hypothesis, post prandial portal insulin and arterial glucose concentrations were compared in (i) intact pigs (IEP), (ii) pigs with gastric canula, (IEP + GC) and (iii) pigs with gastric canula and surgically interrupted EP neurons (XEP + GC) ( n = 8). EP neurons section was achieved by sectioning the connective attachments between the pancreas and the proximal duodenum and the antrum. The test meal (800 ml of glucose 5%) was ingested voluntarily (IEP), or directly introduced into the stomach (IEP + GC, XEP + GC), to discriminate between the cephalic and the intestinal phases of PAIS. PAIS was significantly decreased in IEP + GC compared to IEP (AUC = 59 ± 21.2 vs 18 ± 6.6 μUI/ml/5 min for IEP vs IEP + GC, p = 0.04). PAIS was further nullified in XEP + GC (AUC = − 2 ± 8.1 μUI/ml/5 min). Glycemia was not modified in IEP, IEP + GC or XEP + GC. We conclude that EP neurons are responsible for the intestinal phase of PAIS since it disappeared in XEP + GC.

Oropharyngeal receptors and Fos staining following dehydration and rehydration in the rat

Oropharyngeal receptors and Fos staining following dehydration and rehydration in the rat

Oral sensory stimulation improves glucose tolerance in humans: effects on insulin, C-peptide, and glucagon.

In animals, bypassing the oropharyngeal receptors by intragastric administration of glucose results in glucose intolerance. To determine whether the absence of oral sensory stimulation alters glucose tolerance in humans, we monitored plasma levels of glucose and hormones after intragastric administration of glucose, with and without subjects tasting food. Plasma glucose area under the curve (AUC) was significantly lower after oral sensory stimulation (3,433 +/- 783 vs. 5,643 +/- 1,397 mg.dl-1. 195 min-1; P < 0.03; n = 8). Insulin and C-peptide AUCs were higher during the first one-half of the sampling period (insulin, 5,771 +/- 910 vs. 4,295 +/- 712 microU. ml-1.75 min-1; P < 0.05; C-peptide, 86 +/- 10 vs. 66 +/- 9 ng.ml-1. 75 min-1; P < 0.03) and lower during the second one-half of the sampling period compared with the control condition (1,010 +/- 233 vs. 2,106 microU.ml-1. 120 min-1; P < 0.025; 31 +/- 8 vs. 56 +/- 18 ng.ml-1. 120 min-1; P < 0.05; insulin and C-peptide, respectively). Oral sensory stimulation markedly increased plasma glucagon compared with the control condition (1,258 +/- 621 vs. -2,181 +/- 522 pg.ml-1. 195 min-1; P < 0.002). These data provide evidence in humans that oral sensory stimulation influences glucose metabolism and suggest that the mechanisms elicited by this cephalic stimulation are necessary for normal glucose homeostasis.

Mechanism of drinking-induced inhibition of vasopressin secretion in dehydrated dogs

Ingestion of water stimulates a powerful inhibitory input to secretion of arginine vasopressin (AVP) in many species. A previous study in dogs has suggested that the stimulus arises from activation of oropharyngeal receptors, but the nature of the stimulus is unknown. The objectives of this study were to determine if the taste, osmolality, or temperature of the solution ingested constituted an important element in the inhibitory mechanism and if these same attributes affected the volume ingested in response to 24 h of water deprivation in conscious dogs. Experiments consisted of a control period, a 6-min period of access to fluid, and a 60-min period after drinking, with blood samples taken frequently to assess changes in plasma AVP. Dogs were placed in a sling that allowed them to stand or lie supported with easy access to a bowl. The solutions were water at 20 and 38 degrees C; 0.9% NaCl at 20 and 38 degrees C; 1.8 and 2.7% NaCl at 20 degrees C; 5% glucose and mannitol and 10% mannitol at 20 degrees C; and liquified food at 20 degrees C. In the time-control experiment dogs were allowed to see but not drink water for 6 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic and sympathetic nerve activities of brown adipose tissue in tube-fed rats

To investigate possible contribution of oropharyngeal factors to thermogenesis in brown adipose tissue (BAT), rats were given a liquid diet orally or through a gastric tube for 4-12 days. Tube-fed rats weighed more and had heavier white adipose tissue than orally fed rats, although they were given the same amount of the diet. Triglyceride content of the interscapular BAT was higher in tube-fed rats, but the rate of fatty acid synthesis was lower than those in orally fed rats. Uptake of 2-deoxyglucose (2DG), an index of glucose utilization, in BAT was also lower in tube-fed rats. Surgical sympathetic denervation of BAT reduced both lipogenic activity and 2DG uptake to abolish the differences in these metabolic activities between tube-fed and orally fed rats. Sympathetic nerve activity in the BAT assessed from the turnover rate of norepinephrine in the tissue was lower in tube-fed rats. The results suggest that there is a sympathetically mediated mechanism dependent on afferent input from oropharyngeal receptors to regulate BAT thermogenesis and that greater fattening seen after tube feeding may be attributable to a decreased BAT thermogenesis because of the absence of food-induced sensory stimulation.

Drinking and vasopressin release following central injections of angiotensin II in minipigs.

Angiotensin II (AII; 300 ng) injected into the lateral cerebral ventricle produced significant drinking responses and also stimulated release of lysine vasopressin (LVP) in conscious, water replete, unrestrained minipigs. Plasma LVP concentration, measured by a specific radioimmunoassay, was decreased by drinking. At the end of the experiment the level was inversely proportional to the volume of water drunk in response to the AII, and not to changes in plasma osmolality. These findings suggest that AII-stimulated LVP release is influenced by a negative feed-back mechanism, probably involving oropharyngeal receptors.

Cold water stimulation of oropharyngeal receptors in man inhibits release of vasopressin.

The act of drinking ameliorates thirst and inhibits the secretion of vasopressin before changes in extracellular fluid volume or osmolality in both animals and man. We evaluated whether this reflex inhibition of vasopressin secretion might be due to the presence of oropharyngeal receptors in humans. After dehydration, normal subjects (n = 4) were allowed to suck on ice chips for 30 min. Despite the absence of changes in plasma sodium (Na+) or osmolality, the mean plasma vasopressin level decreased promptly within 10 min from 2.8 to 1.8 pg/mL, and it remained low for 30 min after ice ingestion. When the dehydration protocol was repeated with the subjects receiving 100 mL water (25 C) for 30 min rather than ice chips, plasma vasopressin levels did not change. These data demonstrate that activation of cold-sensitive oropharyngeal receptors results in inhibition of vasopressin secretion independently of osmotic or gastric factors. In a second study 0.2 mL/kg X min 3% NaCl was administered for 90 min as a second stimulus to vasopressin secretion, and ice chips were given during the last 30 min of infusion. Plasma vasopressin levels increased steadily to 3.3 +/- 0.5 (+/- SEM) pg/mL by 45 min, and despite ice ingestion increased further to 4.6 +/- 0.8 pg/mL by 90 min. Consequently, hypertonicity appears to be a stronger stimulus to vasopressin release, since the suppressive effect of stimulation of oropharyngeal receptors with ice was not evident during the NaCl infusion. Finally, no changes in vasopressin levels were found in subjects holding concentrated NaCl solutions in their mouths for 30 min, indicating that the oropharyngeal receptors are not responsive to local changes in osmolality. The presence of such cold-sensitive oropharyngeal receptors may explain the desire of severely dehydrated patients, e.g. patients with diabetes insipidus, for cold liquids.

Comparison of activity in pontine versus medullary neurones during swallowing.

1. On decerebellectomized sheep lightly anaesthetized with fluothane, the activity of 49 neurones in the pontine relay (see Car et al., 1975) was recorded with microelectrodes following stimulation of afferents in the superior laryngeal nerve (SLN), 2. These pontine neurones (PN) exhibited an "initial activity" (one or a few spikes) for stimulation either of the homolateral SLN (35 PN) or glossopharyngeal nerve (14 PN). This initial activity had a latency between 1.5 and 4 msec. When swallowing was induced by SLN stimulation, a later discharge appeared. This "swallowing activity" consisted of a variable burst of spikes. 3. The effect of curarization was tested for 13 PN. It always eliminated the "swallowing activity". 4. A clear antidromic response of 16 PN (26 tested PN) was induced by stimulating the thalamic VPM nucleus. This stimulation failed to elicit an antidromic response in medullary neurones (14 tested) located in the nucleus of the tractus solitarius. 5. It is concluded that PN are probably sensory relay neurones which inform higher nervous centres of the state of oropharyngeal receptors; whereas medullary swallowing neurones are really interneurones involved in the programming of the wallowing motor sequence.

Effects of surface anesthesia on deglutition in man.

AbstractThe importance of sensitivity in the mouth, pharynx and esophagus upon swallowing was studied on 17 healthy volunteers. Intraluminal pressures of the pharynx, pharyngo‐esophageal sphincter and esophagus were synchronously recorded before and after surface anesthesia with lidocaine. Anesthesia of the mucous membrane in sectors of the oral cavity, pharynx or esophagus separately did not cause any objective changes, whereas simultaneous anesthesia of an area consisting of the soft palate, tonsillar pillars, tonsils, base of the tongue and pharynx, caused considerable changes upon swallowing: the coordination between the pharynx and sphincter was disturbed; dysphagia and coughing occurred. Similar dys‐coordinations have been reported earlier from patients with hypopharyn‐geal diverticulum but have not previously been shown experimentally. The changes are probably caused by the mucous membrane's anesthesia inhibiting the discharge of impulses from oropharyngeal receptors.

Erratum: Water Intake without the Act of Drinking

The second sentence of the third paragraph of the report by A. N. Epstein, "Water intake without the act of drinking" [ Science 131, 497 (19 Feb. 1960)], should have read "With this in mind, a chronic gastric tube for rats was developed that is passed through the nasopharynx, thus bypassing the head and oropharyngeal receptors." In the published report, a corrected version of a line from the following sentence, "nasopharyngeal gastric tubes were first," was substituted for the words "nasopharynx, thus bypassing the head...."