Regulation Of Salivary Secretion Research Articles

Alteration of tight junctions during botulinum toxin type A-inhibited salivary secretion.

Tight junctions (TJs) are involved in the regulation of salivary secretion via paracellular pathway. Botulinum toxin type A (BTXA) is widely used for the treatment of hypersecretion diseases such as sialorrhea. This study aimed to investigate the role of TJs in BTXA-inhibited secretion of the submandibular gland (SMG). BTXA was injected into the SMGs of rats, and the same amount of saline was injected as a control. Western blot, real-time PCR, and immunofluorescence staining were used to detect the expression and distribution of TJ proteins. Paracellular permeability was evaluated using the transepithelial electrical resistance (TER) measurements and fluorescent tracer detection in BTXA-stimulated SMG-C6 cells. BTXA injection into the SMGs of rats led to increased expression of claudin (Cldn) -1 and Cldn3. Immunofluorescence staining showed no significant changes in the distribution of TJ proteins. In vitro, BTXA increased the TER values and significantly reduced the permeability of fluorescent tracer, suggesting that BTXA decreased the paracellular permeability. The expression levels of Cldn1, Cldn3, and Cldn4 were upregulated after BTXA treatment. The expression of TJ proteins changed in both animal models and SMG-C6 cells after BTXA treatment, which may contribute to the inhibition of salivary secretion.

Influence of Age-Related Changes in Nitric Oxide Synthase-Expressing Neurons in the Rat Supraoptic Nucleus on Inhibition of Salivary Secretion

Age-related inhibition of salivary secretion has been demonstrated in rats, and the nitric oxide (NO) present in the supraoptic nucleus (SON) and the medial septal area has been reported to play an inhibitory role in the regulation of salivary secretion. In the present study, we investigated the age-related changes occurring in the NO synthase (NOS)-expressing neurons in the SON, which is related to the production of NO, and discussed the interrelation between the age-related changes in the NOS-expressing neurons and the age-related inhibition of salivary secretion. Nissl staining and reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry were performed for young adult and aged rats. Quantitative analysis was also performed using the Nissl-stained and NADPH-d-positive neurons. Although the numbers of the Nissl-stained neurons did not change, significant age-related increases were detected in cell number, cell size and reactive density of the NADPH-d-positive neurons. Therefore, the production of NO in the SON neurons increased with age. We concluded that the age-related increase in the NO in the SON might be a factor that contributes to the age-related inhibition of salivary secretion.

Inhibitory effect of diazepam on muscarinic receptor-stimulated inositol 1,4,5-trisphosphate production in rat parotid acinar cells.

1. This study examined the effect of diazepam (DZP) on phosphoinositide turnover, which plays an important role in the regulation of salivary secretion, in rat parotid acinar cells. 2. DZP (10(-9) M to 10(-5) M), a potent agonist of both central- and peripheral-type benzodiazepine receptors, dose-dependently decreased inositol 1,4,5-trisphosphate IP3 production stimulated by carbachol, a muscarinic receptor agonist, in the cells. 3. DZP produced a maximum inhibitory response at a concentration of 10(-5) M, with IP3 production decreased to 63% of maximal levels. The concentration inducing half maximal inhibition of IP3 production was approximately 3.5 x 10 (-8) M. 4. An inhibitory response to DZP was produced by a short-term pretreatment (<3 min) of the cells and prevented by antagonist and competing ligand for the central- and peripheral-type benzodiazepine receptors, flumazenil and PK 11195, respectively. 5. DZP showed a non-competitive inhibition of carbachol-stimulated IP3 production. It did not directly inhibit the activities of GTP-binding regulatory proteins and phosphatidylinositol 4,5-bisphosphate-specific phospholipase C (PLC) in the parotid gland membranes, though choline chloride inhibited PLC activity. 6. DZP (10(-5) M) attenuated the increase in the intracellular Ca2+ concentration ([Ca(2+)](i)) in the cells following stimulation of the muscarinic and alpha(1)-adrenoceptors. 7. These results suggest that in the parotid acinar cells, DZP inhibits muscarinic receptor-stimulated IP3 production through benzodiazepine receptors and that PLC activity which produces IP3 is inhibited by chloride. The decreases in IP3 and [Ca(2+)](i) in the cells may be connected with the suppression of salivary secretion induced by DZP.

Determination of parotid urea secretion in sheep by means of ultrasonic flow probes and a multifactorial regression analysis.

For determination of the dynamics of parotid urea secretion in conscious sheep, a previously standardized transit time ultrasonic flow metering system was used to measure bilateral parotid flow. Six ewes fed for ad libitum consumption were prepared under halothane anesthesia with ultrasonic probes around both parotid ducts; these ducts were also cannulated orally. After probe encapsulation (8 d), parotid flows were recorded during 24 h, and samples of saliva and blood for urea determination were obtained hourly. Jaw movements were recorded by means of a submandibular balloon to monitor feeding behavior. Urea concentration in parotid saliva was 60 to 74% of that in plasma (a positive linear correlation existed) and was poorly influenced by the parotid flow. The amount of urea secreted with parotid saliva was directly related to the salivation rate. To calculate the urea secretion in parotid saliva, a multiple linear regression model was developed from computer-calculated parotid flows over 1-min periods and plasma urea concentration. The model was accurate because the plot of calculated vs measured values was not significantly different from the line of identity. The daily parotid urea N varied from .35 to 1.02 g among ewes. The higher urea secretion rate found during rumination and eating (1.32+/-.42 and .98 +/-.33 mg/min, respectively) vs. during rest (.60+/-.39 mg/ min, P<.05) was due to higher salivation rates (5.17 +/-1.46, 3.56+/-.90, and 2.04+/-.52 mL/min, respectively, P<.05) rather than to changes in saliva urea concentrations (saliva:plasma urea ratio = .65+/-.04, .67+/-.04, and .68+/-.03, respectively). Of the daily parotid urea output, 40.8% was secreted during rest. The contribution of parotid urea N to the ruminal N pool was relatively small (1.2 to 3.7% of the N intake, which was 23.0 to 33.6 g/d). These techniques allowed direct and precise measurements of parotid urea secretion without disturbing the animal or altering the physiological regulation of salivary secretion.

Neurokinin A in the parotid and submandibular glands of the rat: immunohistochemical localization and effect on protein and peroxidase secretion

An indirect immunofluorescence technique was used to study the distribution of neurokinin A immunoreactive (NKA-IR) nerve fibres in submandibular and parotid glands of the rat. The functional role of neurokinin A on protein and peroxidase secretion in these glands was evaluated by using in vitro methods. In the parotid gland neurokinin A immunoreactive fibres were mainly distributed around the secretory acini, but some were also in evidence around the stromal blood vessels and ducts. The number of the neurokinin A immunoreactive nerve fibres was lower in the submandibular gland than in the parotid gland. They were mainly distributed around the secretory acini and stromal blood vessels and ducts. In vitro, neurokinin A significantly stimulated the release of total amount of released proteins and peroxidase from parotid gland fragments, while in the submandibular gland only the release of peroxidase was increased. By using SDS polyacrylamide gel electrophoresis (SDS-PAGE) specific changes were found in the release of proteins after neurokinin A stimulation. The results of the present study demonstrate that neurokinin A immunoreactive nerve fibres are present in the rat parotid and submandibular glands. Their localization around the secretory elements of the glands and the effect of neurokinin A in vitro experiments indicates that neurokinin A might have a significant role in the regulation of salivary secretion.

Effects of vasoactive intestinal polypeptide on acetylcholine stimulation of rat submandibular gland.

Studies were carried out on the role of vasoactive intestinal polypeptide (VIP) in the regulation of secretion and blood flow in the rat salivary gland. The first experiments to investigate the spontaneous secretory pattern revealed a clear diurnal fluctuation with a significant increase at night, so that the subsequent experiments were performed during the daytime where the secretion was consistently low. Intravenous administration of VIP at a dose smaller than 40 pmole caused a dose-dependent vasodilatory response, but at a high dose such a local effect was hampered by a decrease in systemic blood pressure. VIP potentiated the acetylcholine chloride (AcCho)--evoked salivary secretion, but VIP (0-100 pmole/kg) alone did not cause salivary secretion. Atropine reduced the salivary secretion evoked by AcCho and VIP, and the blood flow change evoked by AcCho. However, the blood flow change evoked by VIP was not affected by atropine. Hexamethonium exerted no significant effect on the response to administration of AcCho or VIP. The results indicate that VIP has a significant vasodilatory action and cooperates with AcCho in the regulation of salivary secretion in the rat, and VIP effects are atropine resistant, as in other species of animals.

Depletion of neuropeptides in rat parotid glands and declining atropine-resistant salivary secretion upon continuous parasympathetic nerve stimulation

In rats the parasympathetic auriculo-temporal nerve on one side was continuously stimulated at 40 Hz for 20–80 min in the presence of adrenergic blockers (dihydroergotamine and propranolol) +/− atropine. During the first 10 min this gave rise to a flow of saliva from the parotid gland that in the atropinized rats amounted to 35% of that found in rats not treated with atropine, while the protein and amylase outputs were 75% of those in non-atropinized rats. The atropine-resistant secretion of fluid and proteins declined to 5–10% of the initial value within 40 min but did not cease completely even after 80 min. The marked reduction in secretory responses was not due to desensitization or exhaustion of the gland cells. The nerve stimulation reduced the parotid gland content of vasoactive intestinal peptide (VIP) and substance P (SP) to approximately 60 and 25% of that of contralateral glands after 20 and 60 min, respectively. The probable explanation for the decline in secretory response seems to be depletion of non-adrenergic, non-cholinergic transmitter(s). The present results suggest that neuropeptides are involved in the regulation of salivary secretion but provide no direct evidence that either VIP or SP is responsible for the atropine-resistant salivary secretion.

Stimulation of salivary secretion by a factor extracted from hypothalamic tissue.

A polypeptide that stimulates an increase in the volume and α-amylase activity of saliva within seconds after intravenous injection into anesthetized rats has been detected and partially purified from bovine and rat hypothalamic tissue. This polypeptide, first noticed after fractionation of bovine hypothalamic extracts on G-75 Sephadex and named sialogen, gives a dose-response curve for volume and α amylase activity of the collected saliva, retainsits activity in test rats pretreated with atropine sulfate, phenoxybenzamine, or propranolol, and is still active in hypophysectomized rats. Purification by cation exchange chromatography on sulfoethyl Sephadex C-25 shows that bovine sialogen is a strongly basic substance. If sialogen proves to be of physiological significance it may function as a neurohormone participating with the nervous system in the regulation of salivary secretion. (Endocrinology 81: 803,1967)

Histochemical appearances of cholinesterase in the submaxillary of sublingual salivary glands of the rat.

DESPITE the researches of Babkin1 and others, no definite conclusions have been reached with regard to the relative part played by the sympathetic and parasympathetic nerve fibres in the regulation of salivary secretion or the exact mode of termination of the fibres in the vicinity of the secretory units of the glands. It was considered that a histochemical study of the distribution of cholinesterase in the sub-maxillary and sublingual salivary glands of the rat might shed light on the problem.

Role of sympathetic nerves in the regulation of salivary secretion.

ArticleRole of Sympathetic Nerves in the Regulation of Salivary SecretionCalvin A. Richins, and Albert KuntzCalvin A. RichinsFrom the Department of Anatomy, Saint Louis University School of Medicine, St. Louis, Missouri, and Albert KuntzFrom the Department of Anatomy, Saint Louis University School of Medicine, St. Louis, MissouriPublished Online:01 Jun 1953https://doi.org/10.1152/ajplegacy.1953.173.3.471MoreSectionsPDF (560 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited BySalivary gland function, development, and regenerationAlejandro M. Chibly, Marit H. Aure, Vaishali N. Patel, and Matthew P. Hoffman17 May 2022 | Physiological Reviews, Vol. 102, No. 3Reflex Sympathetic Dystrophy of the Face: Current Treatment RecommendationsThe Laryngoscope, Vol. 108, No. 3Selective innervation of different target tissues in guinea-pig cranial exocrine glands by sub-populations of parasympathetic and sympathetic neuronsJournal of the Autonomic Nervous System, Vol. 66, No. 1-2The Cervical Sympathetic Nerves in Surgery of the Neck1 October 1991 | Otolaryngology–Head and Neck Surgery, Vol. 105, No. 4Nerve Interactions in Salivary Glands9 November 2016 | Journal of Dental Research, Vol. 66, No. 2Hyperplasia Of The Parotid Gland U.N.S.: A Stress Phenomenon?8 July 2009 | Acta Oto-Laryngologica, Vol. 80, No. 1-6Effects of light and darkness on human parotid salivary flow rate and chemical compositionArchives of Oral Biology, Vol. 18, No. 5Light Deprivation and Parotid Flow in the Human9 November 2016 | Journal of Dental Research, Vol. 51, No. 6The innervation of salivary glands11 November 2011 | Journal of the Royal Microscopical Society, Vol. 86, No. 1Die Physiologie der neurovegetativen RegulationenAction of transmitters on the responsiveness of effector cellsExperientia, Vol. 21, No. 2Adrenergic innervation of the salivary glands in the ratZeitschrift f�r Zellforschung und Mikroskopische Anatomie, Vol. 68, No. 2SECRETORY NERVES OF THE SALIVARY GLANDSSensitivity of the Normal and Denervated Parotid Gland to Chemical AgentsActa Physiologica Scandinavica, Vol. 33, No. 1 More from this issue > Volume 173Issue 3June 1953Pages 471-473 Copyright & PermissionsCopyright © 1953 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1953.173.3.471History Received 25 February 1953 Published online 1 June 1953 Published in print 1 June 1953 Metrics