Inhibition Of Salivary Secretion Research Articles

MicroRNA-mRNA expression profiles and functional network after injection of botulinum toxin type A into submandibular glands

Botulinum toxin type A (BTXA) is effective for the treatment of sialorrhea. MicroRNAs (miRNAs) have significant functions in salivary diseases, but the role of miRNAs during BTXA-inhibited salivary secretion is not yet clear. A total of 19 differentially expressed (DE) miRNAs and 1072 DE mRNAs were identified following BTXA injected into submandibular glands of rats (n = 4) through miRNA sequencing and microarray analysis. Bioinformatic analysis identified that several pathways may be associated with the inhibition of salivary secretion, such as the MAPK signalling pathway, tight junctions, and cytokine-cytokine receptor interaction. We predicted the target genes of DE miRNAs and established the miRNA-mRNA interaction network. The intersection of DE mRNAs and target genes of DE miRNAs was performed and seven mRNAs were obtained: Egr2, Paqr9, Zkscan1, Usp6n, Cyb561a3, Zfhx4, and Clic5. These findings explore the mechanism of BTXA in inhibiting salivary secretion and probably will provide new ideas for clinical application.

Inhibition of salivary secretion by tolterodine transdermal patch.

Tolterodine, a nonselective muscarinic antagonist available only as immediate release (IR) or extended release (ER) oral formulations, is used for the treatment of overactive bladder (OAB). This study aimed to compare the efficacy and extent of dry mouth adverse effects of tolterodine transdermal patch to the oral formulation. The two formulations have been examined through the muscarinic receptor binding tests conducted in bladder and salivary gland tissues and the salivary secretion tests conducted in rats. Comparable average tolterodine blood concentration levels were obtained 3h after oral administration of tolterodine 25mg/kg and 12h after transdermal application of tolterodine patch 6mg/8cm2. While Kd in the bladder tissue increased to a similar degree in both formulations of tolterodine, Kd in the salivary gland increased to a greater degree in the oral formulation. These results indicate that similar degree of inhibitory effects were observed in the bladder for both formulations while less inhibitory effects were observed in the salivary gland with tolterodine transdermal formulation compared to the oral formulation. For assessment of salivary secretion, tolterodine transdermal patch 6mg/8cm2 application resulted in significantly less inhibitory effects than oral tolterodine 25mg/kg. Therefore, this study suggests that tolterodine transdermal patch could be a useful formulation that provides uniform and consistent inhibitory effects to effectively control OAB symptoms with reduced severity of dry mouth in comparison to the oral formulation.

5 ラット視索上核における一酸化窒素合成酵素陽性ニューロンの加齢変化が唾液分泌抑制に及ぼす影響(第512回 大阪歯科学会例会)

5 ラット視索上核における一酸化窒素合成酵素陽性ニューロンの加齢変化が唾液分泌抑制に及ぼす影響(第512回 大阪歯科学会例会)

Diazepam Enhances Production of Diazepam-Binding Inhibitor (DBI), a Negative Saliva Secretion Regulator, Localized in Rat Salivary Gland

Peripheral-type benzodiazepine receptor (PBR) and central-type benzodiazepine receptor (CBR) in salivary gland play a role in the inhibitory regulation of salivary secretion in rodents. Diazepam-binding inhibitor (DBI), an endogenous ligand for PBR, produces neurosteroids, which modulate CBR activity. In this study, we investigated the effect of repetitive administration of diazepam (DZP) on salivary secretion and expression of DBI mRNA and peptide. Moreover, mRNA expression of PBR and pituitary adenylate cyclase–activating polypeptide (PACAP), a transcriptional regulator for DBI promoter, was evaluated after repetitive administration of DZP. Repetitive administration, but not single administration, of 0.4 mg/kg DZP caused inhibition of salivary secretion and enhanced expression of DBI, PACAP, and PBR mRNA in rat salivary gland, with an increase in production of DBI peptide. These results suggest that repetitive administration of DZP stimulates DBI production, which may result in an increase in the suppressive effect of DZP on salivary secretion.

Botulinum toxin in preparation of oral cavity for microsurgical reconstruction

Conclusions. Infiltration of botulinum toxin in the major salivary glands allows a temporary reduction of salivation that begins 8 days afterwards and returns to normal within 2 months. The inhibition of salivary secretion, carried out before the oral cavity reconstructive surgery, could allow a reduction of the incidence of oro-cutaneous fistulas and local complications. Objectives. Saliva stagnation is a risk factor for patients who have to undergo reconstructive microsurgery of the oral cavity, because of fistula formation and local complications in the oral cavity. The authors suggest infiltration of botulinum toxin in the major salivary glands to reduce salivation temporarily during the healing stage. Patients and methods. During the preoperative stage, 20 patients with oral cavity carcinoma who were candidates for microsurgical reconstruction underwent sialoscintigraphy and a quantitative measurement of the salivary secretion. Injection of botulinum toxin was carried out in the salivary glands 4 days before surgery. The saliva quantitative measurement was repeated 3 and 8 days after infiltration, sialoscintigraphy after 15 days. Results. In all cases, the saliva quantitative measurement revealed a reduction of 50% and 70% of the salivary secretion after 72 h and 8 days, respectively. A lower rate of local complications was observed.

ラット視索上核における一酸化窒素合成酵素陽性ニューロンの加齢変化が唾液分泌抑制に及ぼす影響(大阪歯科大学大学院歯学研究科博士(歯学)学位論文内容要旨および論文審査結果要旨の公表)

ラット視索上核における一酸化窒素合成酵素陽性ニューロンの加齢変化が唾液分泌抑制に及ぼす影響(大阪歯科大学大学院歯学研究科博士(歯学)学位論文内容要旨および論文審査結果要旨の公表)

Inhibition of Salivary Secretion by Activation of Cannabinoid Receptors

It is known that marijuana use decreases saliva secretion. Therefore, we hypothesized that cannabinoid receptors (CBs) are located in salivary glands to mediate that effect. In these experiments, we used the submandibular gland (SMG) of male rats, which is one of the major salivary glands. Mammalian tissues contain at least two types of CBs, CB1 and CB2, mainly located in the nervous system and peripheral tissues, respectively. Both receptors are coupled to Gi protein and respond by inhibiting the activity of adenylyl cyclase. We demonstrated that both CB1 and CB2 are present in the SMG, each showing specific localizations. The best-known endocannabinoid is anandamide (AEA), which binds with high affinity to CB1 and CB2. We showed that AEA markedly reduced forskolin-induced increase of cAMP content in vitro. This effect was blocked by AM251 and AM630 (CB1 and CB2 antagonists, respectively), indicating that both receptors are implicated in SMG physiology. In addition, we showed that AEA injected intraglandularly to anesthetized rats inhibited norepinephrine (NE)- and methacholine (MC)-stimulated saliva secretion in vivo and that both AM251 or AM630 prevented the inhibitory action of AEA. Also, the intraglandular injection of AM251 increased saliva secretion induced by lower doses of NE or MC. This increase was synergized after coinjection with AM630. Therefore, we concluded that AEA decreases saliva secretion in the SMG acting through CB1 and CB2 receptors.

Muscarinic receptors and salivary secretion

The release of acetylcholine from parasympathetic nerves and its interaction with muscarinic acetylcholine receptors (mAChRs) regulates many fundamental functions in the periphery (smooth muscle contraction, glandular secretion, modulation of cardiac output) and central nervous system (motor control

Inhibition of salivary secretion by lipopolysaccharide: possible role of prostaglandins.

Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important in the regulation of the function of different organs during infection. A single dose of lipopolysaccharide (LPS; 5 mg/kg ip) within 6 h increased NOS activity (20%) and prostaglandin E (PGE) content (100%) in submandibular glands (SMG) and blocked stimulated salivary secretion in adult male rats. The administration of an iNOS synthesis inhibitor, aminoguanidine (AG), with LPS decreased NOS activity and PGE content. Furthermore, the administration of meloxicam (MLX), an inhibitor of COX-2, blocked the increase in PGE and the production of NO. The incubation of slices of SMG in the presence of 3-morpholinosydnonimine, a donor of NO, increased the release of PGE highly significantly. The incubation of SMG in the presence of a PGE(1) analog (alprostadil) increased the production of NO. These results indicate that LPS activates NOS, leading to NO release, which activates COX, generating PGEs that act back to further activate NOS, causing further generation of PGEs by activation of COX. Because the alprostadil administration inhibited stimulated salivation, LPS-induced inhibition of salivation appears to be caused by increased PGE production. Diminished salivary secretion produces poor oral health; thus the use of COX-2 inhibitors to counteract the effects of inhibited salivation should be considered.

Study of benzodiazepine-induced inhibition of salivary secretion: Effect of intracellular pH on phospholipase C in rat parotid gland membranes

Study of benzodiazepine-induced inhibition of salivary secretion: Effect of intracellular pH on phospholipase C in rat parotid gland membranes

The inhibition of salivary secretion by histamine H2-antagonists--a study on the cat submandibular gland.

The aim of the present work was to establish whether the secretory process can be influenced by histamine H2-receptor antagonists, burimamide and metiamide. These drugs were applied intravenously and the secretion was evoked by the electrical stimulation of the chorda tympani nerve or by carbachol (i.v.). In addition to the measurements of the flow of saliva, the blood flow through the gland was measured in some experiments. Both H2-antagonists significantly reduced the rate of salivary secretion induced by the chorda tympani stimulation. The experiments with burimamide did not permit the calculation of dose-response relationship. From the experiments with metiamide the ED50 was 4.6 mumols/kg and Emax was 30% reduction of secretion. The secretory response to carbachol was not diminished by burimamide. In addition to the effect of metiamide on salivation, the reduction of the blood flow through the gland was observed: the effect on the blood flow was significantly smaller, and slower in onset, than the effect on salivation. These results support the hypothesis that H2-receptors are involved in the process of salivary secretion. Histamine effects on glandular elements seem to be more significant than its effect on the blood vessels.

Intraruminal injection of urea and changes in secretion of parotid saliva in sheep.

1. Sheep were injected with varying doses of urea into the rumen and changes in the amount of saliva secreted from one parotid gland were studied. When the dose of urea was 0.1-0.2 g/kg, the secretion underwent no change. When the dose was 0.3 g/kg, the secretion was inhibited. When the dose was 0.4 or 0.5 g/kg, there was a marked inhibition in the secretion. 2. There was a close relationship between the ammonia level of the jugular blood and the inhibition of salivary secretion. When the ammonia level exceeded approximately 0.28 mmol/l, the secretion was inhibited abruptly. 3. Salivary secretion and rumen movement were inhibited when the blood ammonia level exceeded 0.28 mmol/l, after injection of ammonium acetate into the jugular vein. 4. Based on the results mentioned previously, the mechanism of inhibition on the secretion of parotid saliva is discussed in relation to the domestic ruminant in which urea had been injected into the rumen.

Inhibition of salivary secretion and secretory potentials by g-strophantin, dinitrophenol and cyanide.

The hyperpolarization of the contraluminal acinar cell membrane which takes places when the submandibular gland is stimulated, is called the secretory potential. Much indirect evidence has been presented in favour of the hypothesis that the mechanism of establishment of this potential is due to an active electrogenic chloride transport, and not to a change of the membrane permeability for ions. This transport should be responsible for the formation of the saliva. If this is true, both secretory potentials and secretion should be inhibited to the same degree by metabolic inhibitors. In the present work it was found that the metabolic inhibitors dinitrophenol and cyanide and the cardiac glucoside g‐strophantin (ouabain) had the ability to inhibit completely both secretion and secretory potentials in the perfused cat submandibular gland.

Definition(s) of Anxiety

To the Editor:— The controversy between the clinician Sagebiel and the psychologist Cattell concerning the definition of anxiety (LETTERS, JAMA 190 :859 [Nov 30] 1964) is of epistemological rather than semantic interest. It demonstrates the epistemological inferiority, even uselessness, of the psychologists' approach. Anxiety and fear belong to so-called general feelings ( Gemeingefuhle ). Fear is an atavistic emotional heritage serving protective purposes against a threatening event, impending danger, or risky performance. This psychological emotion is a cortical function with repercussion on the diencephalic autonomic nervous system. Alteration of respiration, pulse rate, or blood pressure; blushing or pallor; inhibition of salivary secretion; or weeping are witness thereof. Anxiety is fear without extrinsic cause, without a substratum, not fear of something. It is an autonomous feeling aroused by intrinsic cortical processes, conscious or subconscious memories and associations originating from past experiences and life situations. It is a pathological outlet of mental processes involved