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.     

Postprandial transformations of enzymatic and hormonal properties of saliva and blood

In 14 volunteers, saliva from both parotid, submandibular and sublingual glands were collected by capsules under stimulation of sialosis with citric acid or alimentary trial breakfast. It was taken immediately and on the 1st and 3rd hours of postprandial response. In saliva and the blood serum, alpha-amylases, trypsin, common protein, thyrotropin, thyroxine, triiodthyronin, luteinizing hormone, follicle-stimulating hormone, prolactin, progesterone, oestradiol and hydrocortisone were assessed by means of immuno-assay technique. All but oestradiol hormones had a lower concentration in the saliva than in the blood serum. The concentration and deficits of hormones and trypsin in saliva of submandibular and sublingual glands is higher, than in saliva of parotid glands, the latter having a higher alpha-amylolytic activity. The share of p-amylase in comparison with s-amylase in saliva of parotid glands is lesser than in saliva of submandibular and sublingual glands. In alimentary stimulation of sialosis, the saliva with higher amylolytic and tryptic activity, higher concentration of thyrotropin and thyroxine was found than under a non-alimentary stimulation. After the 1st and the 3rd hours following a trial breakfast, in response to a non-alimentary stimulation of sialosis the saliva was found to preserve properties of a postprandial saliva.     

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.     

Changes in parotid acinar cells accompanying salivary secretion in rats on sympathetic or parasympathetic nerve stimulation

Morphological and secretory effects of stimulating autonomic nerves have been studied in parotid glands of rats. Sympathetic stimulation evoked a slow flow of saliva which had a high concentration of amylase. After long term sympathetic stimulation secretory granules were heavily depleted from the parotid acinar cells. Parasympathetic stimulation evoked a copious flow of saliva with a low concentration of amylase. However, at high frequency stimulation the total amount of amylase secreted on parasympathetic stimulation was as great or even greater than on symphatetic stimulation, nevertheless, any loss of secretory granules from the acinar cells was very small. It is concluded that secretion of parotid acinar granules in the rat is prinicipally a sympathetic function. Secretion of fluid is more effectively produced by parasympathetic stimulation and much of the amylase in such saliva appears to have arisen from sources other than the secretory granules.     

Early detection in saliva of polypeptides associated to isoproterenol-induced mouse parotid hypertrophy

Chronic administration of isoproterenol (IPR) results in a marked hypertrophy and in the induction of a group of putative proline-rich polypeptides in the mouse parotid glands. Some of these polypeptides (pps C-G) have been considered as molecular markers of the parotid gland enlargement. Given the secretory character of polypeptides C-G, the polypeptide composition of mouse saliva was used to monitor the IPR-induced salivary gland hypertrophy. Whole saliva was collected after an oral administration of pilocarpine (PIL). Under those conditions, PIL provoked a massive salivary secretion both in normal control mice and during the whole course of the IPR-induced gland enlargement. Striking changes in the polypeptide composition of saliva obtained from chronically IPR-stimulated animals were observed. Those changes consisted basically in the appearance and progressive increase in concentration of parotid polypeptides C-G and in the progressive diminution in concentration of a couple of normal salivary polypeptides (polypeptides A-B). The appearance of new polypeptides in saliva could be established unequivocally within the 24 h following the trophic adrenergic stimulation. On the other hand, salivary polypeptides induced in response to a single administration of IPR could be demonstrated as late as 7-9 days after the stimulation. Accordingly, detection of parotid polypeptides C-G in PIL-produced saliva obtained from IPR-stimulated mice has proved to be a highly advantageous method to evaluate salivary gland hypertrophy both at very early stages after the trophic stimulation and late after the occurrence of the trophic episode.     

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.     

Effects of isoflurane anesthesia and pilocarpine on rat parotid saliva flow

The purpose of this study was to investigate the effects of isoflurane on unstimulated and pilocarpine-stimulated parotid saliva secretion. Ten male Sprague-Dawley rats weighing 350-400 g were randomized into two groups, and the saliva flow rate and lag phase were measured at two doses of isoflurane in a crossover study design. Increasing the isoflurane concentration from 1% to 2% was associated with a 19% decrease in saliva secretion rate, and the lag to saliva secretion was increased by 155%. To clarify whether the effect of isoflurane (1.5%) on the parotid flow varied with stimulus intensity, we measured the parotid flow induced by seven different doses of pilocarpine on sham-irradiated rats and rats irradiated with single doses of 15 Gy. A maximal pilocarpine response was obtained with 1.5 mg/kg in both irradiated and sham-irradiated rats; however, the parotid flow of the irradiated rats was 50% slower than that of the sham-irradiated rats. In conclusion, 1.5% isoflurane was found to be a good compromise between proper anesthesia and isoflurane-induced inhibition of saliva secretion. Pilocarpine induces saliva secretion in a dose-dependent matter, with supra-maximal stimulation achieved using 1.5 mg/kg.     

Human Salivary Micro-RNA in Patients with Parotid Salivary Gland Neoplasms

Background

Currently, clinical examination, ultrasound scanning (with or without fine needle aspiration cytology), preoperative CT-scan and MRI are available for the differential diagnosis of parotid gland swelling. A preliminary non-invasive salivary diagnostic tool may be helpful in the clinical decision making process. Altered salivary micro-RNA (miRNA) expression levels have been observed in saliva from patients with various cancers. Therefore, we investigated miRNA expression levels in saliva samples from patients with a parotid gland neoplasm using Human miRNA cards in comparison to controls.

Results

In the discovery phase, eight miRNAs were identified having different expression levels in patients compared to controls. In the validation phase, the differences in miRNA expression levels between patients and controls were confirmed for seven out of eight discovered miRNAs (p < 0.001). A combination of two miRNAs yielded a receiver-operator-characteristics curve with an AUC of 0.94 (95% CI: 0.87–1.00; sensitivity 91%; specificity 86%). Validation of discovered miRNAs in segregated collected parotid saliva revealed that expression of these miRNAs differ between whole saliva and parotid saliva.

Conclusions

A two miRNA combination can predict the presence of a parotid gland neoplasm. Furthermore, this study suggested that the identified, patient-specific, salivary miRNAs were not derived from the parotid gland itself.     

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     

Fluid secretion rates from mouse and rat parotid glands are markedly different following pilocarpine stimulation

1. Parotid saliva production in two commonly employed laboratory animals, mouse and rat, was studied following pilocarpine stimulation. 2. When normalized to body wt, average parotid saliva output rates in mice were 3-4-fold greater than those observed in rats. When parotid salivary flow rates were normalized to gland weight, mice still displayed 2-3-fold higher values than rats. 3. The Na+ and K+ content of parotid saliva showed small differences between the two species, while saliva from rats contained 3-fold higher protein levels than observed with mice.     

Salivation in the red kangaroo (Macropus rufus) during sympathetic nerve stimulation

1. Continuous electrical stimulation at low frequency (5 Hz) and short pulse duration (500 microseconds) of the cervical sympathetic trunk for periods up to 15 min caused no obvious flow from the parotid or mandibular glands of the red kangaroo. 2. Higher frequencies combined with longer pulse durations caused both glands to secrete. Flow reached maximum in less than 3 min and then declined but, on cessation of stimulation, flow increased again for a short period. This flow response may be caused by the interaction of the secretory response with myoepithelial contraction. 3. The parotid saliva had substantially higher protein, phosphate and hydrogen ion concentrations, and lower sodium concentrations than cholinergic parotid saliva. The low pH indicates bicarbonate concentrations far lower than in other sympathetic salivas. 4. The mandibular saliva had higher protein, urea and potassium, and lower chloride and hydrogen concentrations than cholinergic mandibular saliva.     

苦味受体与甜味、鲜味受体具有不同的进化途径

通过生物信息学和系统发育学分析,研究了苦味受体和甜味／鲜味受体的进化途径。结果显示,苦味受体和甜味／鲜味受体在进化上具有远相关,并且具有不同的进化途径,提示这可能是导致这些受体具有不同功能,传导不同味觉的原因。     

Salivary secretion elicited by taste stimulation with umami substances in human adults

Salivary secretion from the parotid gland was measured whenumami substances (monosodium L-glutamatc, disodium 5'-inosinateand disodium 5'-guanylate) were applied to the anterior or posteriorparts of the tongue in human adults. The amount of secretioninduced by a low concentration (0.01 M) of umami substanceswas very small and similar to that elicited by 1 M sucrose.Salivation induced by a high concentration (0.1 M) of umamisubstances was about twice that induced by the low concentration,but less than that induced by 0.1 M NaCl. The volume of secretioninduced by a mixture containing the low concentration of bothmonosodium L-glutamate and disodium 5'-inosinate (or disodium5'-guanylate) approximated the arithmetic sum of secretionsinduced by the individual components, whereas a mixture of thehigh concentration of these substances elicited much less salivationthan the sum of secretions for the components. More copiousflow of parotid saliva tended to be induced from stimulatingthe posterior tongue compared to the anterior tongue. The presentresults are discussed in terms of the taste properties of umamisubstances as shown in previous psychophysical and elcctrophysiologicalstudies.     

The activity of cathepsin D in saliva of cystic fibrosis patients

Cystic fibrosis (CF) is genetically determined illness, which is caused by the mutation in the CFTR gene. CFTR protein is also expressed in epithelial cells of parotid glands, therefore parotid glands are also affected in CF patients. Cathepsin D is one of the proteolitic cascade enzymes. Physiological wearing out result in occurrence of trace quantities of this enzyme in serum and body fluids, including saliva. Among different enzymes, saliva contains cathepsin D (CTSD, EC 3.4.23.5). The aim of this study was to determine cathepsin D activity in mixed saliva in cystic fibrosis patients and healthy controls. The study was performed in a group of 26 CF patients (10F, 16M). The results obtained in CF group was compared with the results of thirty healthy subjects (12F, 14M). From each subject 8 ml of mixed saliva was obtained: before and after the stimulation of saliva excretion using paraffin pledgets. Protein and glycoprotein content was assessed using Winzler's method. Protein concentration in controls and CF group before stimulation of excretion was 1.15+/-0.714 mg/mL and 1.54+/-0.925 mg/mL. After stimulation protein concentration in saliva has lowered to 0.88+/-0.77 mg/mL in CF group and 1.24+/-1.213 mg/mL in controls. Glycoprotein concentration in controls and in CF group was respectively: before stimulation 1.08+/-0.271 mg/mL and 1.05+/-0.344 mg/mL; after stimulation 0.92+/-0.292 mg/mL and 0.86+/-0.283 mg/mL. The activity of CTSD in controls was 45.9+/-24.98 Tyr nmol/mL/4h before stimulation and 109.3+/-56.94 Tyr nmol/mL/4h after stimulation of excretion. In CF group CTSD activity before stimulation was 134.5+/-81.80 Tyr nmol/mL/4h and after stimulation 134.4+/-62.18 Tyr nmol/mL/4h. Comparing the CTSD activity in both groups statistically significant difference has been revealed in samples collected before stimulation of excretion (p=0.013). The activity of cathepsin D in saliva of cystic fibrosis patient is significantly higher than in healthy controls before the stimulation of excretion with paraffin pledgets.     

The good taste of peptides

The taste of peptides is seldom one of the most relevant issues when one considers the many important biological functions of this class of molecules. However, peptides generally do have a taste, covering essentially the entire range of established taste modalities: sweet, bitter, umami, sour and salty. The last two modalities cannot be attributed to peptides as such because they are due to the presence of charged terminals and/or charged side chains, thus reflecting only the zwitterionic nature of these compounds and/or the nature of some side chains but not the electronic and/or conformational features of a specific peptide. The other three tastes, that is, sweet, umami and bitter, are represented by different families of peptides. This review describes the main peptides with a sweet, umami or bitter taste and their relationship with food acceptance or rejection. Particular emphasis will be given to the sweet taste modality, owing to the practical and scientific relevance of aspartame, the well‐known sweetener, and to the theoretical importance of sweet proteins, the most potent peptide sweet molecules. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

Effect of parotid submandibular and sublingual saliva on wound healing in rats.

1. The effectiveness of wound licking with parotid, submandibular or sublingual saliva on wound healing was evaluated in selectively sialadenectomized rats. 2. The rate of healing of experimentally induced cutaneous wounds was evaluated macroscopically by photography at 0, 2, 4 and 6 days after surgery. 3. Sialadenectomy of all major glands significantly slowed down wound healing compared to sham-operated controls. 4. Parotid licking had no effect compared to controls; submandibular licking and sublingual licking appeared to be very effective. 5. The results suggest that saliva promotes wound healing in experimentally induced cutaneous wounds by communal licking; this is a result of the submandibular and sublingual saliva and not the parotid saliva.     

Clinical trial with inactivated hepatitis A vaccine and recommendations for its use.

OBJECTIVE--To compare the reactogenicity and immunogenicity of an inactivated hepatitis A vaccine in two different immunisation schedules. DESIGN--Randomised trial. SETTING--One London teaching hospital. SUBJECTS--104 healthy adult volunteers (71 men, 33 women aged 19-60). INTERVENTIONS--Hepatitis A vaccine to group 1 (54 volunteers) at 0, 1, and 2 months and to group 2 (50) at 0, 1, and 6 months. MAIN OUTCOME MEASURES--Symptoms at and after each dose; liver function, hepatitis A virus specific serum immune response; and responses in saliva and parotid fluid in immunised volunteers and subjects with natural immunity. RESULTS--The vaccine was well tolerated; 97% (96/99) and 100% of those immunised developed serum antibody after one and two doses of vaccine respectively. Geometric mean titres increased progressively after each dose and were significantly higher in men but not women in group 2 after the third dose (ratio between geometric mean titres 0.265, 95% confidence interval 0.18 to 0.39; p less than 0.001). At one year this group-sex interaction was absent; geometric mean titres for both sexes were significantly higher in group 2 (ratio 0.330, 0.227 to 0.478; p less than 0.0001). Antibody responses were not significantly different between the groups at two years. Compared with naturally infected subjects immunised volunteers developed poor or undetectable virus specific IgG and IgA responses in saliva and parotid fluid. CONCLUSIONS--The vaccine was safe and highly immunogenic, and the differences in the immune responses in saliva and parotid fluid are unlikely to affect its efficacy.     

Chloride concentration of rat parotid saliva evoked by electrical stimulation of parasympathetic or sympathetic nerves with or without antagonists

Chloride (Cl) of saliva evoked by electrical stimulation of the parasympathetic nerve to parotid gland was from two to seven times higher than that elicited with sympathetic nerve stimulation; [Cl] remained elevated (125-135 mEq/liter) for 60 min of parasympathetic nerve stimulation, whereas Cl of sympathetically evoked saliva decreased from high levels of 58 to 15 to 20 mEq/liter. The administration of propranolol, the beta-adrenergic antagonist, 20 min prior to initiation of sympathetic nerve stimulation resulted in saliva with Cl of 100 mEq/liter; when phentolamine, the alpha-adrenergic antagonist was administered prior to sympathetic nerve stimulation, [Cl] was 48-35 mEq/liter. Values with the beta-agonist, isoproterenol, were about 35 mEq/liter, whereas phenylephrine, an alpha-adrenergic agonist, evoked saliva with Cl ranging from 113 to 85 mEq/liter. Flow rate was very high with parasympathetic nerve stimulation and low with sympathetic nerve stimulation, but [Cl] with beta-blockade was not flow dependent: flow was very low but Cl high. Cl secretion is principally regulated by activation of cholinergic and alpha-adrenergic receptors.     

Salivary myeloperoxidase of young adult humans

Leukocytes, principally polymorphonuclear leukocytes (PMNs), enter the oral cavity where they release a portion of their constituents, including myeloperoxidase, into oral fluids. A greater number of PMNs in the oral cavity are associated with oral inflammation. However, the quantitative contribution of the PMN to oral fluids, including saliva, during various conditions is poorly understood. An assay method based on the adsorbance loss at 278 nm from the reaction of the myeloperoxidase product hypochlorous acid with monochlorodimedon to yield dichlorodimedon was developed for the quantitation of salivary myeloperoxidase. Myeloperoxidase was determined in supernatants of whole saliva obtained at low and moderate flow rates and in parotid saliva collected during moderate and pronounced stimulation from young adults with minimal oral inflammation. The greatest myeloperoxidase activity was in whole saliva supernatants collected at low flow rates where PMN products have an opportunity to accumulate. Lesser quantities of myeloperoxidase were found in both the whole saliva supernatants and parotid saliva obtained at the faster flow rates. Low flow rate whole saliva supernatants contained about 25% of the myeloperoxidase in the PMNs which enter the oral cavity. Myeloperoxidase is responsible for a significant portion (15-20%) of the total peroxidase activity in supernatants of whole saliva obtained at low flow rates. Preliminary results indicate that young adults with phenytoin-associated gingival overgrowth or who smoke have more myeloperoxidase activity in low flow rate whole saliva.