Parotid Salivary Secretion Research Articles

Nerve‐Evoked Secretion of Immunoglobulin a in Relation to other Proteins by Parotid Glands in Anaesthetized Rat

Secretion of fluid and proteins by salivary cells is under the control of parasympathetic and sympathetic autonomic nerves. In a recent study we have shown that, in the rat submandibular gland, autonomic nerves can also increase the secretion of IgA, a product of plasma cells secreted into saliva as SIgA (IgA bound to Secretory Component, the cleaved poly-immunoglobulin receptor). The present study aimed to determine if parotid secretion of SIgA is increased by autonomic nerves and to compare SIgA secretion with other parotid proteins stored and secreted by acinar and ductal cells. Assay of IgA in saliva evoked by parasympathetic nerve stimulation immediately following an extended rest period under anaesthesia indicated that it had been secreted into intraductal saliva in the absence of stimulation during the rest period. The mean rate of unstimulated IgA secretion (2.77+/-0.28 microg min(-1) g(-1)) and the 2.5-fold increase in IgA secretion evoked by parasympathetic stimulation were similar to results found previously in the rat submandibular gland. Sympathetic nerve stimulation increased SIgA secretion 2.7-fold, much less than in the submandibular gland. SDS-PAGE and Western blot analysis with anti-IgA and anti-Secretory Component antibodies confirmed that SIgA was the predominant form of IgA in saliva. Acinar-derived amylase and ductal-derived tissue kallikrein were more profoundly increased by parasympathetic and particularly sympathetic stimulation than SIgA. Overall, the results of the present study indicate that SIgA forms a prominent component of unstimulated parotid salivary protein secretion and that its secretion is similarly increased by stimulation of either autonomic nerve supply. The secretion of other parotid salivary proteins that are synthesized and stored by acinar or ductal cells is upregulated to a much greater extent by parasympathetic and particularly sympathetic stimulation.

1. 食餌の性状および高浸透圧刺激によるラット耳下腺唾液分泌変化(第 60 回九州歯科学会総会講演抄録)

1. 食餌の性状および高浸透圧刺激によるラット耳下腺唾液分泌変化(第 60 回九州歯科学会総会講演抄録)

Renal hemodialysis patients: oral, salivary, dental and periodontal findings in 105 adult cases.

A study of the dental, periodontal, oral mucosal and salivary condition of adult patients with chronic renal failure (CRF) receiving hemodialysis (HD). A total of 105 patients on HD were studied, together with 53 healthy age and sex-matched controls. Indices employed included carious, absent and obturated teeth index (CAO index), plaque index, calculus index and loss of periodontal attachment. Whole and parotid salivary secretions were also measured. The CAO index was not significantly higher among HD patients than controls (14.9 +/- 8.7 vs 13.3 +/- 7.9, respectively; t = 1.1; P = 0.3). However, plaque and calculus indices were significantly higher in HD patients (2.1 +/- 0.8 and 2.3 +/- 0.6, respectively) than controls (1.3 +/- 0.8 and 1.6 +/- 0.9) (P < 0.001). Loss of periodontal attachment was similar in both groups (4.9 +/- 2.5 vs 4.2 +/- 2.5 in the HD patients and controls, respectively) (t = 1.8; P = 0.07). There was no more oral mucosal pathology in HD patients than in controls (chi-square = 5.8; P = 0.3). Stimulated salivary secretion was significantly higher in controls than HD patients for both whole (t = -5.2; P < 0.001) and parotid (t = -2.6; P = 0.01) salivas. The results show significantly higher plaque and calculus indices and lower salivary secretion among the HD patients than in healthy controls.

Modulation by somatostatin of rat parotid salivary secretion stimulated by cholinergic, adrenergic and peptidergic agents

Although it is well known that somatostatin (SRIF) modulates several digestive functions, there are only a few reports about its effect on the salivary glands. Here, the action of SRIF parotid secretion was studied, in vivo and in vitro, in male Wistar rats. In vivo SRIF infusion (35 μg/kg per hr) inhibited the parotid flow rate stimulated by methacholine, substance P and noradrenaline. The isoprenaline-stimulated flow rate was also decreased by SRIF, but only at highest dose of the secretory agent. Total protein and amylase secretion were studied. SRIF inhibited the total protein secretion stimulated by the above-mentioned agents, except that by isoprenaline. SRIF did not inhibit in vivo amylase secretion. In order to avoid flow-rate interference with total protein and amylase measurements, in vitro experiments were performed. SRIF (25 nM) strongly inhibited the total protein release stimulated by methacholine (5.1 μM), noradrenaline (19 μM), and substance P (10 μM). The inhibitory effect was not raised by the absence of calcium in the incubation medium. However, in vitro amylase release was not affected by SRIF. It was concluded that SRIF modulates rat parotid secretion stimulated by cholinergic, adrenergic and peptidergic agents, acting on any step in the calcium pathway.

Increased major salivary gland secretion in familial dysautonomia.

Familial dysautonomia (FD), an autosomal recessive peripheral nervous system disorder, affects almost exclusively children of Jewish Ashkenazi origin and causes profound generalized autonomic dysfunction. Excessive drooling is frequent and is traditionally attributed to swallowing difficulties. Although true hypersalivation has been postulated, no quantitative assessment of the salivary secretion rate has yet been reported. The authors determined this rate in 13 children with FD and 28 healthy controls. Resting parotid, submandibular/sublingual and unstimulated whole salivary secretion rates were significantly elevated in children with FD. The known relation of salivary function with age was found in controls only. This apparently major contribution of salivary hyperfunction to excessive drooling in FD may be attributable to salivary gland denervation supersensitivity, as this mechanism is present in the cardiovascular system and the pupil in FD.

Cholinergic regulation of amylase gene expression in the rat parotid gland. Inhibition by two distinct post-transcriptional mechanisms.

Stimulation of the beta-adrenergic or cholinergic muscarinic receptors are the principal mechanisms by which parotid salivary secretion is regulated in vivo. In this study we have examined the effects of cholinergic stimulation on amylase gene expression in dispersed rat parotid cells. [3H]Leucine incorporation into amylase and total protein was inhibited by carbamylcholine. Within 5 min of its addition, 10 microM carbamylcholine induced a 50-60% reduction in the rate of amylase synthesis which was sustained for more than 2 h. Blockade of the muscarinic receptor with atropine 8 min after addition of 10 microM carbamylcholine reversed the carbamylcholine-induced inhibition of amylase synthesis. When cells were exposed to carbamylcholine for 2 h before addition of atropine, there was only a slight reversal of inhibition. Carbamylcholine had no significant effect on the rate of total RNA synthesis but caused a progressive loss of amylase mRNA. After 2 h, amylase mRNA in cells treated with 10 microM carbamylcholine was 46% of control levels. Actinomycin D (5 micrograms/ml) lowered amylase mRNA by 8%; cycloheximide and phorbol 12-myristate 13-acetate had no effect. Isoprenaline (isoproterenol; at a concentration of 10 microM), which is an inducer of amylase gene transcription, elevated the amylase mRNA content by 30% after 2h. The calcium ionophore A23187 mimicked the effect of carbamylcholine by inhibiting [3H]leucine incorporation into amylase and lowering amylase mRNA content. The results suggest that acute stimulation of the muscarinic cholinergic receptor inhibits amylase biosynthesis in parotid cells not only by rapid attenuation of translation but also by causing a gradual loss of amylase mRNA, apparently by a Ca(2+)-dependent destabilization of the mRNA.

Effects of beta-adrenergic antagonists on salivary secretory function in individuals of different ages.

The purpose of this study was to assess the effects of chronic beta-adrenergic antagonists on parotid and submandibular gland secretions in men and women of different ages. Unstimulated and stimulated saliva flow rates, total protein concentrations, and protein secretion rates were compared from medicated (various beta-antagonists, n = 25) and control (n = 60) subjects. Age-related decreases were found in unstimulated parotid saliva flow rate (p = .011) and protein secretion rate (p = .04), unstimulated submandibular salivary flow rate (p = .005) and protein secretion rate (p = .010), and in stimulated submandibular flow rate (p = .002) and protein secretion rate (p = .006). A drug-related effect was observed only in unstimulated parotid salivary flow (p = .033) and protein secretion rate (p = .04) from medicated subjects. Results from this study indicate that age and beta-adrenergic blockade alter salivary glandular function, but their effects differ with the type of salivary secretion examined.

Oral retention of glucose at pharmacologically reduced salivary flow in man

The aim was to study the influence of mouthrinses with glucose, at concentrations ranging from 1 to 50%, on oral retention at two different locations in the oral cavity. Salivary secretion was reduced in 10 subjects by injection of methylscopolamine nitrate submucosally. The volunteers were randomly assigned to rinse with 10 ml of either 1%, 10%, or 50% glucose solution for 30 s, after which measurements of glucose concentration and parotid salivary secretion rate were performed during a 10-min period. The results showed higher salivary glucose levels vestibularly than sublingually. The difference in glucose retention between the two locations increased when the salivary flow rate recovered. The relationship between secretion rate and area under the curve for glucose measured sublingually, but not in the vestibule, was bilinear.

Effect of Salivary Components on Dissolution Rates of Carbonated Apatites

Salivary pellicle has been reported to retard the acid-induced demineralization of dental enamel. However, this effect has not been quantified, nor has the direct protective effect of pellicle on carbonated apatite dissolution been elucidated. We have developed a model capable of further studying these questions. Well-characterized synthetic ceramic carbonated apatite discs were pretreated with parotid or whole salivary secretions for 18 h or 7 days and then challenged with 0.1 mol/l acetate, pH 5.0, in a dissolution apparatus. Surface dissolution rates were compared to those from the same carbonated apatites with no saliva pretreatment. Pellicles formed from whole and parotid saliva in vitro and whole saliva in vivo were capable of reducing surface dissolution rates of ceramic carbonated apatites by up to 83% but the degree of this reduction was dependent on the type of saliva and the conditions of pretreatment.

Chemical Involution of the Equine Parotid Salivary Gland

The efficacy of eliminating parotid salivary secretions by retrograde infusion of 10% formalin, 2% chlorhexidine, or 2% or 3% silver nitrate solutions was evaluated in 10 horses. Solutions were kept within the parotid salivary gland for 90 seconds after infusion through parotid duct cannulae and then allowed to drain freely. Severed parotid ducts and surgical incisions were left to heal by second intention. All agents eliminated glandular secretions. There was less necrosis and suppurative inflammation after formalin infusion than after chlorhexidine and silver nitrate. Silver nitrate (2% and 3%) caused the most necrosis and inflammation.

Effect of phosphate-regulating hormones on plasma composition, cardiovascular function, and parotid salivary phosphate secretion in red kangaroos (Macropus rufus)

The effects of administration of phosphate-regulating hormones on plasma composition, cardiovascular function, and secretion of phosphate and other electrolytes in parotid saliva were investigated in anesthetized red kangaroos. Plasma [PO4] was elevated by intravenous injections of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) at 5 or 12.5 nmol/12 hr for 72 hr but was unaltered by intravenous or intracarotid infusion of either salmon or porcine calcitonins at rates up to 3.2 IU min-1 for 60 min or by intracarotid infusions of the 1-34 amino acid fragments of rat, human, or bovine parathyroid hormones (PTH(1-34) at 350-460 pmol/min for 60 min. Plasma [Ca] fell during high-rate calcitonin infusion and rose during 1,25(OH)2D3 administration. PTH(1-34) infusion did not alter plasma [Ca] but did lower plasma [K] and arterial blood pressure and elevated heart rate and hematocrit. Salivary [PO4] and [Ca] and secretion rates were unaffected by the calcitonin infusions, by PTH(1-34) infusions, or by 1,25(OH)2D3 injection. Plasma and salivary concentrations of other ions were unaltered. These data provide evidence that kangaroo tissue can recognize and respond to all three types of phosphate-regulating hormones despite the peptides being foreign; however, the parotid gland of kangaroos, unlike the parotids of rats and sheep, did not respond and presumably lacks some component of the receptor-secretion couplings for these hormones. This independence of salivary PO4 secretion from hormonal regulation may be one of several adaptations which ensure relatively stable and adequate phosphate delivery to the foregut microorganisms despite an unreliable phosphorus intake in the natural diet.

Diminished Submandibular Salivary Flow in Dementia of the Alzheimer Type

Dementia of the Alzheimer Type (DAT) is the most common type of dementia among the elderly. Alzheimer's disease is a major public health problem, yet little is known about the potential oral consequences of the disease. Because saliva is believed to be essential for the preservation of oral health and function, salivary gland fluid output was evaluated in a population of essentially healthy patients with early-stage DAT. Unstimulated and stimulated parotid and submandibular salivary gland secretions were collected from 28 nonmedicated and otherwise healthy DAT patients, and 35 age-matched healthy controls. Submandibular saliva flow rates were significantly lower among the patients with DAT compared to controls, while parotid flow rates did not differ. The results suggest a selective impairment in submandibular gland function in essentially healthy patients with early-stage DAT.

The effects of a liquid diet on initial and sustained, stimulated parotid salivary secretion and on parotid structure in the rat

Adult male rats were maintained on a nutritionally adequate liquid diet, or laboratory chow and water (controls), for 7 days. They were then anaesthetized and parotid flow was recorded after isoprenaline or pilocarpine stimulation, each collected over two, timed sampling periods—an initial 5 min and a subsequent 15 min. The isoprenaline-induced flow rates in liquid diet rats were reduced to 45 and 30% of those in control rats for the first and subsequent samples respectively ( p < 0.02). After pilocarpine stimulation there were no significant differences in the first samples, but in the subsequent samples the flow rate in liquid diet rats was reduced to 54% of that in controls ( p < 0.001). The parotid gland weights were reduced by 35% in liquid diet rats compared to controls ( p < 0.05). On computerized planimetric analysis, parotids (from rats that had not been given secretagogues) had significantly smaller mean acinar areas, mean acinar profile perimeters and mean acinar transection diameters after liquid feeding ( p < 0.001). The findings support the notion that there is a functional reserve capacity available in atrophied glands to support the relatively fast flow that occurs on initial stimulation but which becomes exhausted during sustained stimulation. This exhaustion occurs more severely and more rapidly in the low-volume, protein-rich saliva elicited by sympathomimetic stimulation than in the high-volume, low-protein saliva formed in response to parasympathomimetic stimulation.

Effects of acute ethanol administration on stimulated parotid secretion in the rat.

Young adult male rats previously never exposed to ethanol were given a single dose of 4 ml of 35% (v/v) ethanol in water by direct intragastric intubation (approximate weight related dose = 5.2 g/kg). Control rats were given distilled water in the same volume by the same route or were given no intragastric fluids. After administration of Valium-Hypnorm anesthesia, parotid salivary secretion was stimulated by subcutaneous pilocarpine HCI (10 mg/kg), and accurately timed samples were collected. No differences were recorded in the rate of salivary flow during the initial (5-min) high-flow phase of secretion, but during the subsequent 25-min phase of secretion the output in ethanol-treated rats was depressed by 60% compared to controls (p less than 0.01). Furthermore, electrolyte analyses of this saliva indicated that salivary ductal resorptive activity might be diminished in the presence of high blood ethanol. However, when rats were previously habitually exposed to ethanol at a twice daily dose of 4 ml of 35% (v/v) ethanol in water, the inhibitory action of acute ethanol administration was abolished. Moreover, in these rats there was significantly depressed [Na+] in both high-flow and low-flow saliva samples (p less than 0.01) with little change in [Na+] occurring at higher flow rates. This suggests the possibility of enhanced ductal resorption developing in rats exposed to long-term ethanol feeding.

中耳手術後の耳下腺唾液流量の測定

Parotid salivary flow in 53 patients with chronic otitis media and in 20 normal control subjects was measured pre- and postoperatively. There were no statistically significant differences between the right and left parotids. Neither chronic otitis media nor cholesteatoma disturbed parotid salivary flow. Resection of Jacobson's nerve or the chorda tympani reduced parotid salivary flow. Resection of both nerves doubled the reduction of parotid salivary flow. These results suggest that the chorda tympani affects parotid secretion. The chorda tympani may contain secretory fibers to the parotid gland or autonomic nerve fibers which influence the parotid salivary secretion. However, this assumption is difficult to confirm, partly because of species differences or even differences in a single species of the innervations to the parotid gland. In our study contralateral parotid salivary flow did not reveal significant changes postoperatively. Postoperative reduction of parotid salivary flow was nearly fully restored approximately 9 months after middle ear surgery.

5-Hydroxytryptamine Modulation of Rat Parotid Salivary Gland Secretion

5-Hydroxytryptamine (5-HT) has been reported to produce significant responses in blowfly salivary glands, but little information is available concerning its action on mammalian salivary glands. When 5-HT (0.1 mumol/L to 10 mumol/L) is infused i.a. into anesthetized rats, no salivary secretion is obtained from either parotid or submandibular glands. However, when 5-HT is infused along with a threshold concentration of acetylcholine (0.1 mmol/L), potentiation of parotid secretory response is seen with 5-HT (1 mumol/L, 260% increase; 10 mumol/L, 146% increase). Substance P (0.3 mumol/L) combined with 5-HT (1 mumol/L) also resulted in a potentiation of parotid secretion (160% increase). Protein and calcium concentrations were not altered during such treatments. No potentiation of submandibular secretion was noted. Experiments in vitro with parotid cell aggregates exhibited no potentiation associated with the combined use of 5-HT and carbachol, as measured by amylase secretion and inositol trisphosphate accumulation. The experiments indicate that 5-HT substantially modulates parotid salivary secretion in vivo; however, the in vitro findings suggest that 5-HT does not act directly on surface glandular receptors. The magnitude of the in vivo potentiation could very well implicate circulating or released 5-HT as a physiological modulator of endogenous neurotransmitter action.

Submandibular and parotid salivary secretion after electrolytic lesioning of the brainstem nucleus parvocellularis in the rat

The present study, in consonance with recent anatomical investigations, demonstrates that activation of the nucleus parvocellularis in the rat evokes a potent hypersecretory effect in the submandibular and sublingual (S-S) salivary glands. Furthermore, electrolytic lesioning of this region in conjunction with peripheral removal of the parotid glands is followed by an increase in the number of drinking responses in the presence of dry food. Such prandial drinking behavior is only observed after total impairment of salivation (i.e, removal of the S-S + parotid glands), thus suggesting that the parvocellularis lesion led to a marked deficit in S-S salivary secretion (Experiment 1). On the other hand, the activation of the nucleus parvocellularis was seen to have only a slight effect on parotid salivary secretion. Electrolytic lesions to this zone, when associated with peripheral removal of the S-S glands, failed to induce prandiality, suggesting that the parvocellularis nucleus exerted a low level of control over parotid salivary secretion (Experiment 2). These results are interpreted as functional proof of the relationship between the parvocellularis reticular formation and the superior salivatory nucleus in the secretion of S-S saliva.

Molecular basis of salivary proline-rich protein and peptide synthesis: cell-free translations and processing of human and macaque statherin mRNAs and partial amino acid sequence of their signal peptides.

Acidic proline-rich phosphoproteins and phosphopeptides are abundant components of parotid and submandibular salivary secretions in man and in the subhuman primate, Macaca fascicularis. The major acidic proline-rich proteins and the proline-rich phosphopeptide, statherin, of man and macaques have been shown to be potent inhibitors of calcium phosphate precipitation and are thought to function in the oral environment by maintaining saliva supersaturated with respect to calcium phosphate salts. Little is known about the biosynthesis of these proline-rich phosphoproteins and peptides, and the aim of the present work was to determine the structural relationship between statherin precursors and native human and macaque statherin. RNA was isolated from human submandibular gland, and poly(A+) mRNA was selected by affinity chromatography on oligo(dT) cellulose and translated in a reticulocyte lysate. Electrophoretic analysis of the translation products revealed that this mRNA directed the synthesis of a large number of polypeptides with Mrs ranging from 5000 to 70,000. Immunoprecipitates, prepared with an antiserum directed against human statherin, contained a single component with a Mr of 7800, approximately 2000 daltons larger than native statherin. Radiosequencing of the in vitro precursor of statherin in immunoprecipitates demonstrated the presence of a 19-residue signal peptide. These results suggest that statherin is derived from a unique structural gene, and does not result from proteolytic processing of a large polyprotein precursor.

Effects of Substance P and Substance P Antagonists on Rat Salivary Secretion

The intra-arterial infusion of substance P produced dose-related responses of both parotid and submandibular salivary secretion in anesthetized rats. The substance P-induced secretion in both glands was inhibited by the substance P analogues [D-Arg1, D-Trp7.9, Leu11]-substance P and [D-Arg1, D-Pro2, D-Trp7.9, Leu11]-substance P, but not by [D-Pro2, D-Trp7,9]-substance P. The profiles of protein and calcium levels obtained with substance P-induced salivary secretion for both glands were similar to those produced by acetylcholine stimulation and were not altered by the substance P analogues.

Autonomic mechanisms underlying capsaicin induced oral sensations and salivation in man.

The effects of capsaicin, citric acid and nicotine applied to the apex or radix of the tongue on taste sensations and salivation were studied in relation to the presence of substance P immunoreactive neurones in man. Application of capsaicin (30 micron) to the apex of the tongue or to the palatinal mucosa, but not to the radix of the tongue, caused a reproducible burning sensation and salivation from the submandibular-sublingual and parotid glands. The salivation response to capsaicin was reduced by methylscopolamine pretreatment. Similar levels of substance P immunoreactivity were present in the lingual apex and radix area (including vallate papillae) of man, while in the cat about 4 times higher levels of substance P immunoreactivity were present in the vallate papillae than in the lingual apex. Immunohistochemistry showed that in the cat many substance P immunoreactive nerves were associated with the taste buds of the vallate papillae, while in man substance P immunoreactive fibres were only seen penetrating into the epithelium of the lingual apex. In addition some subepithelial blood vessels in all regions were surrounded by substance P immunoreactive nerves in both cat and man. Citric acid application to the tongue apex caused both submandibular-sublingual and parotid salivary secretion concomitant with a burning sensation. Salivary secretion was also seen after citric acid application to the radix of the tongue. This response was associated with a sour taste. The salivation response to citric acid was not significantly reduced by methylscopolamine pretreatment. Lingual apex application of nicotine was associated with a sweet taste and a small rise in salivary secretion rate. This response was not significantly reduced by methylscopolamine. In conclusion, the sensitivity to capsaicin of the human tongue is restricted to the apex portion. This is in parallel with the occurrence of intraepithelial substance P immunoreactive nerve fibres. Capsaicin induced salivary secretion seems mainly to be mediated via parasympathetic, cholinergic reflex mechanisms. Citric acid and nicotine induced salivation responses are comparatively more resistant to methylscopolamine pretreatment.