The influence of PTH, calcium gluconate and EDTA on the parotid saliva in the goat

1. The role of exogenous parathyroid hormone (PTH) and stimulation or inhibition of endogenous hormone release, on the parotid gland of normal and thyroparathyroidectomized (t.x.p.t.x.) goats was studied. 2. The intravenous infusion of PTH and EDTA produced a transitory rise in saliva flow rate in intact animals. In t.x.p.t.x. goats the flow of saliva decreased transiently throughout the infusion. 3. The calcium levels in parotid saliva was unchanged throughout the infusion of PTH, EDTA, calcium gluconate both alone or with propranolol, in either intact or t.x.p.t.x. animals. 4. The parathyroid hormone infusion caused an increase in salivary phosphate concentration in both intact and operated goats. The effects of PTH upon the salivary flow and concentration of P are discussed.     

Effects of chronic clonidine administration on parasympathetic-evoked rat saliva.

Effects of chronic administration of clonidine on parasympathetic-evoked saliva from both parotid and submandibular glands were investigated. Clonidine at 1 mg/kg/day for 5 or 7 days caused a significant reduction in the salivary secretion (flow rate and total volume) evoked by parasympathetic nerve stimulation of parotid but not submandibular glands. Ion concentrations (Na, K and Ca) of parasympathetically nerve-evoked parotid saliva were not altered. However, the total protein concentration as well as output, amylase activity, and output of such saliva were markedly increased. Possible mechanisms for clonidine-induced increase in nerve-elicited salivary protein concentration include release of neuropeptides, and changes in adrenergic receptor binding which need further study.     

Low parotid saliva calmodulin in patients with taste and smell dysfunction

Parotid saliva calmodulin was found both in 32 normal volunteers and in 60 patients with taste and smell dysfunction; salivary calmodulin concentration was significantly lower in the patients than in the volunteers. There were no differences in salivary calmodulin concentration with respect to age, sex, or salivary flow rate in either normal volunteers or patients. When patients were categorized by diagnosis, calmodulin concentration was found to be decreased in all patient groups. The concentration of calmodulin in saliva was about 10 times that found in serum, suggesting that the parotid gland is a major source of this protein.     

Modulating effects of prostaglandins on parasympathetic-mediated secretory activities of rat salivary glands

Exogenously administered PGE1 or PGE2, like atropine, markedly decreased both the flow and calcium concentration of parasympathetically evoked rat parotid saliva; PGF2 alpha was less effective. Despite the fact that prostaglandins greatly reduced the Ca concentration of nerve-evoked saliva, they did not change the glandular Ca concentration of either control or parasympathetically stimulated parotid glands. Prostaglandins (20 micrograms/kg, i.a.) decreased the Na or K concentration of nerve-evoked parotid saliva, but at lower doses had no significant effect. PGE1, PGE2, PGF2 alpha or atropine markedly decreased flow rates of similarly evoked rat submandibular saliva. Prostaglandins and atropine, however, decreased the Na concentration and increased the K concentration of parasympathetically evoked submandibular saliva. PGF2 alpha, like atropine, increased the Ca concentration of such saliva. Drug vehicle, ethanol, slightly decreased the flow of both parotid and submandibular saliva but not the ion secretion, Endogenous prostaglandins themselves may not play a role in secretory activities during parasympathetic nerve stimulation of rat salivary glands, since administration of indomethacin, and inhibitor of prostaglandin biosynthesis, prior to or during nerve stimulation did not significantly alter nerve-evoked salivary secretion, The mechanisms by which prostaglandins modulate secretory responses of salivary glands during parasympathetic stimulation are not understood.     

The role of the autonomic nervous system in the depression of parotid salivary secretion during hyperkalaemia in conscious sheep.

The rate of flow and electrolyte concentration of parotid saliva were measured before, during and after intravenous and contralateral intracarotid infusion of KCl (0.5 mol.1(-1)) and NaCl (0.5 mol.1(-1)) at 385-625 mumol. min(-1) for 40 min into 5 sheep. In intact conscious sheep contralateral intracarotid infusion of KCl caused marked depression of salivary secretion in all experiments whereas infusion of NaCl had no consistent effect on flow. Intravenous infusion of KCl into the intact conscious sheep caused a slight depression of salivary secretion but minimum flow was significantly higher than that during intracarotid infusion. When the sheep were anaesthetized salivary flow rates were low and contralateral intracarotid infusion of KCl either had no effect on flow or caused an increase in flow. After ipsilateral cervical sympathectomy contralateral intracarotid infusion of KCl into the conscious sheep caused a marked depression of salivary flow similar to that occurring when the sheep were intact. After section of the secretomotor nerve of the gland salivary flow rates were low and contralateral intracarotid infusion of KC1 had no effect on flow. The salivary flow responses of the sheep were consistent, regardless of whether the KCl infusions were given within 24 h or 1-2 weeks after cervical sympathectomy or secretomotor nerve section. Salivary sodium concentration was negatively correlated with salivary flow in all experiments. It was concluded that potassium acted at a site located in the head but by direct action on the salivary gland. The depression of salivary secretion by hyperkalaemia resulted from a decline in neural activity in the parasympathetic secretomotor innervation of the parotid gland.     

Radioisotopic and biochemical determination of salivary secretion after long term psychotropic therapy

The aim of this work was to investigate the effect of prolonged psychotropic therapy (neuroleptics and antidepressants over 5 yr on salivary secretion. The flow rate in the parotid and submandibular glands were measured separately by scintigraphy. Flow rates, total protein concentration and total IgA level were determined in the unstimulated saliva in 30 control subjects and 73 patients treated with psychotropic drugs. As evidenced by measurement of flow rates and scintigraphy, psychotropic therapy reduced the unstimulated salivary secretion from parotid glands and to a lesser extent from submandibular gland. The scintigraphic study showed a lower response to stimulation in patients than controls.     

Modulating effects of prostaglandins on parasympathetic-mediated secretory activities of rat salivary glands

Exogenously administered PGE₁ or PGE₂, like atropine, markedly decreased both the flow and calcium concentration of parasympathetically evoked rat parotid saliva: PGF_2α was less effective. Despite the fact that prostaglandins greatly reduced the Ca concentration of nerve-evoked saliva, they did not change the glandular Ca concentration of either control or parasympathetically stimulated parotid glands. Prostaglandins (20 μg/kg, i.a.) decreased the Na or K concentration of nerve-evoked parotid saliva, but at lower doses had no significant effect. PGE₁, PGE₂, PGF_2α or atropine markedly decreased flow rates of similarly evoked rat submandibular saliva. Prostaglandins and atropine, however, decreased the Na concentration and increased the K concentration of parasympathetically evoked submandibular saliva. PGF_2α, like atropine, increased the Ca concentration of such saliva. Drug vehicle, ethanol, slightly decreased the flow of both parotid and submandibular saliva but not the ion secretion. Endogenous prostaglandins themselves may not play a role in a secretory activities during parasympathetic nerve stimulation of rat salivary glands, since administration of indomethacin, an inhibitor of prostaglandins biosynthesis, prior to or during nerve stimulation did not significantly alter nerve-evoked salivary secretion. The mechanisms by which prostaglandins modulate secretory responses of salivary glands during parasympathetic stimulation are not understood.     

The salivary flow rate and composition of whole and parotid resting and stimulated saliva in young and old healthy subjects

Resting and stimulated whole and parotid salivary composition and flow rate were examined in 63 healthy volunteers. No significant differences were found between the young and old in secretion rates and salivary concentrations of sodium, potassium, calcium, magnesium, and total protein. The activity of amylase in the resting and stimulated parotid saliva was significantly lower in the old.     

Analysis of parotid and mixed saliva in Roe deer (Capreolus capreolus L.)

In ruminants, different functions have been ascribed to the different salivary glands according to the feeding type. In this context, possible adaptations of salivary functions were investigated regarding the secretion of various proteins by different types of salivary glands. To yield uncontaminated parotid saliva in large quantities, a non-surgical method has been developed. Parotid gland secretions were collected via endoscopic placement of guide wires into each parotid duct, which were subsequently used for placement of collection catheters. Salivary flow was stimulated by intra-glandular administration of the parasympathomimetic compound pilocarpine-hydrochloride into the parotid gland. Mixed saliva (excluding parotid saliva) was collected into sterile tubes by normal outflow during the sampling of parotid saliva. The total flow volume, flow rate and the content of proteins as well as of several ions (Na⁺, K⁺, Ca²⁺, inorganic phosphate) of both types of saliva were measured in sheep, fallow deer and roe deer. Roe deer secreted the highest amount of total salivary proteins relative to body mass [mg/kg body mass] and the highest relative volume [ml/10 min/kg body mass], both in parotid and mixed saliva, of all ruminant species examined. Additionally, the protein profile and the tannin-binding properties of parotid and mixed saliva in roe deer were investigated. Parotid saliva bound almost twice as much tannin as mixed saliva, underlining the importance of yielding uncontaminated parotid saliva for tannin-binding studies. Accepted: 6 January 1998     

The role of protein kinase C on amylase secretion from rat parotid gland

The activities of Ca2+.phospholipid-dependent protein kinase (protein kinase C) in rat salivary gland were assayed using synthetic peptide syntide-2(Pro-Leu-Ala-Arg-Thr-Leu-Ser-Val-Ala-Gly-Leu-Pro-Gly-Lys- Lys) as substrate. Levels of the protein kinase C were less than 0.05 units/g in the parotid and submandibular glands. The protein kinase C inhibitor, H-7, inhibited amylase secretion from rat parotid gland stimulated by PMA or the combination of phosphatidylserine and 1,2-diolein. The results supported the hypothesis of the secretory mechanism that protein kinase C mediates amylase secretion in rat parotid glands.     

Relationships between plasma composition and parotid salivary composition and secretion rates in the potoroine marsupials,Aepyprymnus rufescens and Potorous tridactylus

Summary Parotid salivation was investigated in two species of potoroine marsupial, Aepyprymnus rufescens and Potorous tridactylus to ascertain flow rates and composition, the buffer capacity of the saliva with respect to possible dependence of these animals on foregut fermentation, and the similarity of anion excretion patterns to those of the kangaroo parotid. Under anaesthesia neither species secreted spontaneously and secretion was stimulated by intravenous infusion of carbachol, bethanechol and isoprenaline. Under cholinergic stimulation in Aepyprymnus, the concentrations of Na, Cl, HCO₃ and osmolality were positively correlated with flow rate, whereas K, Mg, PO₄, H⁺ and urea were negatively correlated with flow. Amylase activity and the concentrations of protein and Ca showed no consistent relation to flow. Relative to Aepyprymnus, saliva of Potorous had much lower amylase activity and amylase activity per gram protein, lower concentrations of urea and Ca, and higher Na. Protein, K and HCO₃ concentrations were similar in both species. The plasma of both species had similar electrolyte concentrations, but Potorous had lower protein, urea, osmolality and amylase activity. Plasma amylase activity in Aepyprymnus rose during cholinergic stimulation to levels in excess of rodent plasma. Isoprenaline infusion in Aepyprymnus increased salivary amylase activity and concentrations of protein, Ca, HCO₃ and PO₄, and reduced the concentrations of Cl and H⁺. The patterns of anion excretion in the two potoroine marsupials were dissimilar to those of the kangaroo parotid suggesting that parotid fluid secretion is not HCO₃ driven to the same extent as that of kangaroos. Buffer anion concentrations and secretion rates were similar to koalas and low relative to kangaroos, indicating that these potoroines do not rely on foregut fermentation.Abbreviations bw body weight - SEM standard error of mean - VFA volatile fatty acids     

Modulation of PKCdelta tyrosine phosphorylation and activity in salivary and PC-12 cells by Src kinases

Protein kinase C (PKC) delta becomes tyrosine phosphorylated in rat parotid acinar cells exposed to muscarinic and substance P receptor agonists, which initiate fluid secretion in this salivary cell. Here we examine the signaling components of PKCdelta tyrosine phosphorylation and effects of phosphorylation on PKCdelta activity. Carbachol- and substance P-promoted increases in PKCdelta tyrosine phosphorylation were blocked by inhibiting phospholipase C (PLC) but not by blocking intracellular Ca2+ concentration elevation, suggesting that diacylglycerol, rather than D-myo-inositol 1,4,5-trisphosphate production, positively modulated this phosphorylation. Stimuli-dependent increases in PKCdelta activity in parotid and PC-12 cells were blocked in vivo by inhibitors of Src tyrosine kinases. Dephosphorylation of tyrosine residues by PTP1B, a protein tyrosine phosphatase, reduced the enhanced PKCdelta activity. Lipid cofactors modified the tyrosine phosphorylation-dependent PKCdelta activation. Two PKCdelta regulatory sites (Thr-505 and Ser-662) were constitutively phosphorylated in unstimulated parotid cells, and these phosphorylations were not altered by stimuli that increased PKCdelta tyrosine phosphorylation. These results demonstrate that PKCdelta activity is positively modulated by tyrosine phosphorylation in parotid and PC-12 cells and suggest that PLC-dependent effects of secretagogues on salivary cells involve Src-related kinases.     

Sorbitol Gum in Xerostomics: The Effects on Dental Plaque pH and Salivary Flow Rates1

Adequate salivary flow is important for patient comfort and maintenance of oral health. Xerostomia, or dry mouth, is a common clinical complaint. Masticatory and gustatory activity can stimulate salivary flow from functional salivary tissue and the use of sugarless mints and gums have been recommended to individuals who complain of xerostomia, but there are minimum clinical data. A clinical study assessing the effect on salivary flow rates and dental plaque pH of a sorbitol-sweetened chewing gum in subjects with the complaint of xerostomia was conducted. The chewing of the gum in this present study stimulated salivary flow in the subjects with xerostomia. Statistically significant stimulated whole mouth and parotid salivary flow rate increases were found when compared to unstimulated whole mouth and parotid salivary flow rates. Chewing of the sorbitol-sweetened gum also effectively reduced the drop in pH seen following the exposure to a fermentable carbohydrate. The findings of this present study indicate that chewing of a sorbitol-sweetened gum may be of benefit to patients with the complaint of xerostomia.     

A functional and chemical study of radiation effects on rat parotid and submandibular/sublingual glands.

The aim of this study was to monitor composition and rate of secretion of rat parotid and submandibular/sublingual saliva following local single doses of X-rays ranging from 5 to 20 Gy. Pilocarpine-stimulated samples of parotid and submandibular/sublingual saliva were simultaneously collected with miniaturized Lashley cups before and 1-30 days after irradiation. The lag phase (period between injection of pilocarpine and start of the secretion) and flow rate were recorded and the concentrations of sodium, potassium, calcium, phosphate, and amylase were measured. With increasing dose and time, the salivary flow rate as well as sodium concentration decreased, while potassium concentrations increased throughout the follow-up period. The lag phase and the concentration of amylase reached their maximum at 3 and 10 days after irradiation, respectively. The changes in lag phase and flow rate were most obvious after doses of 15 or 20 Gy and showed a great similarity for parotid and submandibular/sublingual saliva. No dose-response relationship was observed for the changes in concentrations of calcium and phosphate. It is concluded that for radiation doses of 10 Gy and above, irreversible changes (lag phase, flow rate, potassium, sodium) were observed. A saturation of the irradiation effects (lag phase, flow rate) seems to exist at doses larger than 15 Gy. No significant differences were observed between the radiation-induced functional changes in parotid and submandibular/sublingual salivary gland tissue.     

Salivary secretion induced by substance P

Secretion of fluid, ions, and amylase from parotid and submaxillary glands of rat, induced by intravenous injection of substance P (SP), was examined. The action of SP on salivary glands, like physalaemin, resembled that of cholinergic stimulation. While SP-evoked salivary flow from both glands was blocked by atropine, atropine did not modify composition of SP-evoked saliva. The present study suggests that salivary secretion and secretion of ions and amylase evoked by SP are mediated via SP-sensitive cholinergic receptors and specific SP receptors, respectively.     

Salivary secretion during selective β-adrenoreceptor stimulation and blockade in the parotid gland of red kangaroos,<Emphasis Type="Italic"> Macropus rufus</Emphasis>

Intracarotid infusions of noradrenaline (0.3 nmol.kg(-1) x min(-1)) stimulated salivary fluid secretion and caused increases in salivary concentrations of protein, potassium. magnesium. chloride and phosphate, and decreases in bicarbonate. These effects of intracarotid noradrenaline were not reduced by simultaneous intracarotid infusion of phentolamine (3.0 nmol.kg(-1) x min(-1)) but were significantly greater than the responses accompanying intravenous noradrenaline infusion. Concomitant administration of the beta-antagonist, CGP20712A, were much more effective in blocking the noradrenaline-induced changes in salivary composition than equimolar infusions of the beta2-antagonist, ICI118551, thereby confirming the presence of beta1-adrenoreceptors. Intracarotid infusion of salbutamol at 0.6 nmol x kg(-1) x min(-1) and 6.0 nmol x kg(-1) x min(-1) caused increasing but qualitatively similar changes in salivary composition to intracarotid noradrenaline but was less effective than noradrenaline in augmenting salivary protein release. Equimolar intravenous infusions of salbutamol and noradrenaline were equally potent in altering salivary electrolyte concentrations but salbutamol by this route had less effect on protein release and fluid secretion. Concurrent intravenous and intracarotid infusions of beta1-(CGP) and beta2-(ICI) antagonists with intracarotid salbutamol showed that the beta2-antagonist was more potent than the beta1-antagonist by the intracarotid route thereby demonstrating the presence of glandular beta2-receptors and eliminating the possibility that the response to salbutamol was due totally by reflex increases in general sympathetic tone triggered by lowered blood pressure. It was concluded that the kangaroo parotid has functional beta1- and beta2-adrenoreceptor subtypes in endpieces whereas the data provide little support for either adrenoreceptor subtype being present in the excurrent duct system.     

Role of the Accessory Parotid Gland in the Etiology of Parotitis: Statistical Analysis of Sialographic Features

This retrospective study aimed to identify if the existence of the accessory parotid gland correlated with the etiology of parotitis. This may aid the development of better treatment strategies in the future. Sialographic features of cases with parotitis and healthy subjects were reviewed. The chi-square test was used to compare the incidence of accessory parotid gland between the groups. The Student’s t test was used to compare the length of Stensen’s duct, the length from the orifice to the confluence of the accessory duct, and the angle between the accessory duct and Stensen’s duct between the groups. The incidence of accessory parotid gland in patients with parotitis was 71.8% (28/39), which was significantly higher than that in healthy subjects (P = 0.005). Patients with parotitis had a longer Stensen’s duct than healthy subjects (P = 0.003). There was no significant difference in the length from the orifice to the confluence of the accessory duct or the angle between the accessory duct and Stensen’s duct (P = 0.136 and 0.511, respectively) between the groups.The accessory parotid gland might play a role in the pathogenesis of parotitis. The existence of an accessory parotid gland is likely to interfere with salivary flow. Computational fluid dynamics analysis of salivary flow in the ductal system would be useful in future etiologic studies on parotitis.     

Effect of lithium on secretory factors and growth stimulation by bombesin in rat pancreas and salivary glands

Lithium, a drug of choice in bipolar affective disorders, also affects the metabolism and cell proliferation in a diverse array of organisms. In this study, we investigated the effect of lithium on bombesin-mediated function in excretion and growth of the pancreas and the salivary glands. The weight, protein content, amylase concentration and salivary flow rate of the pancreas, parotid and the submandibular glands were determined in male Wistar rats after consumption of either water or lithium chloride (600 mg/l) for 14 days and each group received s.c. injection of either saline or bombesin (10 microg/kg) during the last 4 days of experiment. Our results revealed that administration of bombesin in lithium-treated group not only suppressed pancreas and parotid weight augmentation due to bombesin, but also significantly decreased pancreas growth. Chronic lithium consumption significantly inhibited the protein content augmentation due to bombesin in the salivary glands. Getting bombesin, as well as saline in lithium-treated group, resulted in notable decrease in salivary protein content. Protein content of pancreatic gland increased considerably in the bombesin-injected groups either treated with saline or lithium. In conclusion, the stimulatory effect of bombesin on the growth and protein content of the pancreas and the salivary gland was inhibited by lithium. Lithium seems to be a potent inhibitor of growth factors induced by bombesin probably through inhibiting phosphatidylinositol 4,5,bisphosphate hydrolysis.     

Unexpected beta adrenergic effects of the antitumor agent, cyclocytidine, on rat salivary glands.

In addition to its potent antileukemic properties, cyclocytidine has a sialogogue action that depends on stimulation of beta adrenergic ereceptors of salivary glands. Furthermore, when chronically administered (for 3 days), cyclocytidine caused enlargement of parotid and submaxillary glands and heart that resembled the hypertrophy caused by chronic isoproterenol administration. The salivas evoked by cyclocytidine also closely resembled those evoked by isoproterenol, and were extremely viscous, and high in K+, (121 plus or minus 5.6, for submaxillary, and 42 plus or minus 2.9, for parotid), low in flow rate (0.007 mg/min times mg) and parotid saliva contained high concentrations of amylase (805 plus or minus 33 mg/mg gland). Cyclocytidine also caused marked emptying of parotid gland amylase. The cyclocytidine-induced salivary flow and gland emptying of amylase were prevented for 90 min when propranolol (but not dibenzyline or atropine) was administered prior to injection of the cyclocytidine. In addition, when the superior cervical ganglion was acutely removed, administration of cyclocytidine elicited salivary flow from the denervated as well as the innervated glands. These findings suggest that cyclocytidine does not affect salivary glands through indirect central or ganglionic actions. Cyclocytidine action does not exclusively involve beta receptors, since even in the presence of propranolol, secretory flow was evident after 90 min but when dibenzyline was given with the propranolol, complete blockade of cyclocytidine-stimulated saliva was effected. The dominant effect is, however, a beta adrenergic one. The undesirable side effects of cyclocytidine (parotid pain, postural hypotension, and cardiac hypertrophy) probably stem chiefly from its beta adrenergic properties and might be eliminated (or at least modified) by administration of propranolol with the cyclocytidine.     

The effect of carbonic anhydrase inhibitors on secretion by the parotid and mandibular glands of red kangaroos Macropus rufus

Summary The effects of carbonic anhydrase inhibitors on secretion by macropodine parotid and mandibular glands were investigated using anaesthetized red kangaroos. In the parotid gland, acetazolamide (500 mol·l^-1) reduced a stable acetylcholine-evoked, half-maximal flow rate of 2.02±0.034 to 0.27±0.023 ml·min^-1 (87% reduction). Concurrently, salivary bicarbonate concentration and secretion fell (129.4±1.46 to 80.9±1.63 mmol·l^-1 and 264.8±7.96 to 22.3±2.30 mol·min^-1, respectively), phosphate and chloride concentrations rose (14.0±0.79 to 27.6±0.85 mmol·l^-1 and 5.6±0.25 to 27.5±1.32 mmol·l^-1, respectively), sodium concentration and osmolality were unaltered, and potassium concentration fell (8.8±0.33 to 6.4±0.29 mmol·l^-1). High-rate cholinergic stimulation during acetazolamide blockade was unable to increase salivary flow beyond 11±0.9% of that for equivalent unblocked control stimulation. However, superimposition of isoprenaline infusion on the acetylcholine stimulation caused a three-fold increase in the blocked flow rate. These treatments were accompanied by small increases in salivary phosphate and chloride concentrations but not bicarbonate concentration. Methazolamide infusion caused similar changes in parotid secretion. In the mandibular gland, acetazolamide infusion had no effect on salivary flow rate during either low- or high-level acetylcholine stimulation. Acetazolamide caused no alterrations in salivary electrolyte secretion at low flow rates, but curtailed the rise in bicarbonate concentration associated with high-level acetylcholine stimulation. Acetazolamide administration did not affect the increase in salivary flow rate associated with isoprenaline infusion, but did block the concomitant increase in bicarbonate concentration and secretion substantially. It was concluded that neither cholinergic nor adrenergic stimulation of mandibular fluid secretion depends on secretion of bicarbonate derived from catalysed hydration of CO₂, but a substantial proportion of the increase in bicarbonate secretion during isoprenaline administration, which is probably ductal in origin, is so dependent. In contrast to other salivary glands, including the ovine parotid, fluid secretion by the kangaroo parotid gland during cholinergic stimulation is largely dependent (about 90%) on secretion of bicarbonate derived from hydration of CO₂ catalysed by glandular carbonic anhydrase. Fluid secretion during adrenergic stimulation is not bicarbonate dependent.Abbreviations b.w. body weight - PAH p-aminohippurate - PCO₂ partial pressure carbon dioxide - PCO₂ partial pressure of oxygen