Imipramine Increases Norepinephrine and Serotonin in the Salivary Glands of Rats.

Xerostomia induced by antidepressants such as imipramine has long been thought to be due to their anticholinergic effects. However, even antidepressants with low anticholinergic effects may have a high incidence of xerostomia. In salivary glands, norepinephrine activates alpha-adrenergic receptors in blood vessels and beta-adrenergic receptors in acinar cells, respectively, causing a decrease in the blood flow and an increase in the protein secretion, resulting in the secretion of viscous saliva with low water content and high protein content.

d-Serine Increases Release of Acetylcholine in Rat Submandibular Glands.

d-serine has been observed in submandibular gland tissue in rats, but its functions remain to be clarified. Oral administration of d-serine, but not l-serine, increased its concentrations in the submandibular gland and pilocarpine-induced salivary secretion. In vivo microdialysis was used to collect the d- and l-enantiomers of amino acids from local interstitial fluid in the rat submandibular gland.

Free d-Amino Acids in Salivary Gland in Rat.

Free d-amino acids, which are enantiomers of l-amino acids, are found in mammals, including humans, and play an important role in a range of physiological functions in the central nervous system and peripheral tissues. Several d-amino acids have been observed in saliva, but their origin and the enzymes involved in their metabolism and catabolism remain to be clarified. In the present study, large amounts of d-aspartic acid and small amounts of d-serine and d-alanine were detected in all three major salivary glands in rat.

In Vivo Monitoring of Acetylcholine Release from Nerve Endings in Salivary Gland.

A microdialysis technique was used to monitor acetylcholine levels in the local interstitial fluid in rat submandibular glands, with the aim of determining parasympathetic nerve activity in vivo. The dialysis probe housed a 10 × 0.22 mm semipermeable membrane (molecular weight cutoffs: 50,000 Da).

The effects of 2,3-dimercapto-1-propanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the nephrotoxicity in the mouse during repeated cisplatin (CDDP) treatments.

Previously, we reported that specific lower dose of sodium 2,3-dimercapto-1-propanesulfonic acid (DMPS) which is an antidote to heavy metal intoxication, inversely enhanced cisplatin (CDDP)-induced antitumor activity to S-180 cell-bearing mouse. This activity was only weak with meso-2,3-dimercaptosuccinic acid (DMSA), however. This study investigated the effects of lower doses of DMPS or DMSA on the nephrotoxicity and kinetics of CDDP.

Biocompatibility of a titanium dioxide-coating method for denture base acrylic resin.

Objectives: Ease of denture cleaning is of paramount importance in geriatric patients and those with limited dexterity. We have previously investigated methods of coating dentures with titanium dioxide (TiO ) and reported the effects (self-cleaning and antibacterial) of such treatments in in vitro studies. This study was to verify the biocompatibility of a TiO -coated acrylic resin produced by the new coating method with spray-coating technique.

mRNA expression and localization of LPS-induced β-defensin isoforms in rat salivary glands.

β-defensins are small, cationic peptides with broad-spectrum antimicrobial activity that are produced by mucosal epithelia. However, little is known about the expression of β-defensins in the major salivary glands. The purpose of this study was to characterize expression of rat β-defensin-1 (RBD-1) and -2 (RBD-2) mRNA within the major salivary glands together with the effect of injection of intraductal lipopolysaccharide (LPS) on that expression.

Effect of three peptidase inhibitors on antinociceptive potential and toxicity with intracerebroventricular administration of dynorphin A (1-17) or (1-13) in the rat.

Purpose: The N- and C-terminal regions of dynorphin (Dyn) A (1-17) activate opioid and N-methyl-D-aspartate receptors, respectively. Earlier studies demonstrated that Dyn-converting enzyme cleaved Dyn A (1-17) mainly at the Arg(6)-Arg(7) bond, resulting in the production of N- and C-terminal region peptide fragments, and that this enzyme was not inhibited by a mixture of the three peptidase inhibitors (PIs) amastatin (A), captopril (C), and phosphoramidon (P). The purpose of the present study was to evaluate antinociceptive potential and toxicity with intracerebroventricular administration of Dyn A (1-17) or (1-13) under pretreatment with a mixture of A, C, and P and/or Dyn-converting enzyme inhibitor (p-hydroxymercuribenzoate).

Potentiation of [Met5]enkephalin-induced antinociception by mixture of three peptidase inhibitors in rat.

Purpose: Previous in vitro studies have shown that degradation of opioid peptides during incubation with cerebral membrane preparations is almost completely prevented by a mixture of three peptidase inhibitors (PIs), namely, amastatin, captopril, and phosphoramidon. In the present in vivo study, we evaluate the effects of intrathecal administration of these PIs on antinociception by [Met(5)]enkephalin (ME) or PIs themselves.

Methods: Drugs were administered into the thoracolumbar level of the spinal cord in the intrathecal space in rat.

Immunolocalization and distribution of functional temperature-sensitive TRP channels in salivary glands.

Transient receptor potential (TRP) cation channels are unique cellular sensors involved in multiple cellular functions. Their role in salivary secretion remains to be elucidated. The expression and localization of temperature-sensitive TRP channels in salivary (submandibular, sublingual and parotid) glands were analyzed by immunohistochemistry and quantitative real-time reverse transcription plus the polymerase chain reaction (RT-PCR).

Increase in antinociceptive effect of [leu5]enkephalin after intrathecal administration of mixture of three peptidase inhibitors.

Objective: Previous in vitro studies have shown that the degradation of [Leu5]enkephalin during incubation with cerebral membrane preparations is almost completely prevented by a mixture of three peptidase inhibitors such as amastatin, captopril, and phosphoramidon. The present in vivo study was performed to examine the antinociceptive effect of [Leu5]enkephalin administered intrathecally under pretreatment with these three peptidase inhibitors.

Methods: A tail-flick test was used to determine the nociceptive threshold after administration of [Leu5]enkephalin.

Methamphetamine-withdrawal stress activates PACAP-DBI pathway in rat salivary gland, resulting in inhibition of salivary secretion.

The purpose of this study was to investigate activation of inhibitory regulation pathways by methamphetamine (METH)-withdrawal stress in rat salivary gland. Our previous study showed that METH-withdrawal stress activated steroid biosynthesis and that pregnenolone produced during the early stage of this process inhibited salivary secretion. However, how this type of stress inhibits salivary secretion and the activation pathway of steroid biosynthesis in salivary gland remain to be clarified.

Rat submandibular gland perfusion method for clarifying inhibitory regulation of GABAA receptor.

GABA is an inhibitory transmitter found in rat salivary gland. However, the inhibitory potential of GABA on salivary secretion is unclear. Using an in vivo cannulation method, intraperitoneal administration of GABA was ineffective in the absence of gabaculine, a GABA transaminase inhibitor, on pilocarpine-induced salivary secretion, suggesting that GABA was rendered metabolically inactive before reaching the salivary gland.

Proteomic analysis of lipopolysaccharide-treated submandibular gland in rat.

We investigated changes in the protein profile of submandibular gland (SMG) with inflammation induced by exposure to lipopolysaccharide (LPS) with the aim of identifying potential molecular markers of injured gland. Lipopolysaccharide (2.5µg) was directly administered into rat SMG unilaterally by retrograde ductal injection.

Modulation of benzodiazepine receptor, adrenoceptor and muscarinic receptor by diazepam in rat parotid gland.

This study investigated the influence of diazepam on the binding characteristics of adrenoceptor, muscarinic and benzodiazepine receptors in rat parotid gland membrane using a radioligand binding assay. At a concentration of >10(-6)M, diazepam competed with [(3)H]dihydroalprenolol for β-adrenoceptor, but not [(3)H]prazosin for α-adrenoceptor or [(3)H]quinuclidinyl benzilate for muscarinic receptor. Continuous administration of diazepam at doses of 0.

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.

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.

Pregnenolone biosynthesis in the rat salivary gland and its inhibitory effect on secretion.

Pregnenolone (PRG), a major neurosteroid, suppressed carbachol-induced salivary secretion in perfused submandibular gland in rats. These effects were enhanced and depressed by agonistic muscimol (MUS) and antagonistic bicuculline to the γ-aminobutyric acid A receptor (GABA(A)-R), respectively. In contrast, PRG-sulfate, a sulfate-conjugated PRG metabolite, antagonized the suppressive effects of MUS, resulting in upregulation of salivary secretion.

Paradoxical effect of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on enhancing antitumor activity of cisplatin in ascites sarcoma 180 cells.

We investigated the enhancing effect of two metal-chelating compounds, 2,3-dimercapto-1-propanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA), on the antitumor activity of cisplatin (CDDP). In the in vivo experiments, DMPS showed a clear synergistic effect and significantly enhanced the antitumor activity of CDDP in terms of survival and life span in mice transplanted with ascites sarcoma 180 cells (S180 cells) at a dose of <100 micromol/kg, s.c.

Co-operative effect between gamma-aminobutyric acid A receptors and central-type benzodiazepine receptors on amylase release in rat parotid acinar cells.

We investigated the inhibitory role of gamma-aminobutyric acid A (GABA(A)) receptors on amylase release and the evidence for functional coupling with central-type benzodiazepine receptors in rat parotid acinar cells. Muscimol and GABA decreased isoprenaline-induced amylase release. This effect was blocked by bicuculline, a GABA(A)-receptor antagonist, and enhanced by clonazepam, a central-type benzodiazepine-receptor agonist, and diazepam, a central- and peripheral-type benzodiazepine-receptor agonist.

Evaluation of high-performance liquid chromatography and mass spectrometry method for pharmacokinetic study of local anesthetic ropivacaine in plasma.

We studied the viability of high-performance liquid chromatography and mass spectrometry (LC/MS) as a selective and sensitive analytical method for measuring blood concentrations of the local anesthetic ropivacaine. Ropivacaine was effectively separated using a reverse-phase column and monitored at 275 m/z ion. The LC/MS method allowed measurement of concentrations of ropivacaine of lower than 75 ng/mL.

Immunohistochemical study on GABAergic system in salivary glands.

Gamma-aminobutyric acid (GABA) and its receptors are found in the central nervous system and several peripheral tissues. The purpose of this study was to determine the expression and distribution of GABA and glutamate decarboxylase (GAD), a GABA biosynthetic enzyme, in rat salivary gland. Western blot and real time quantitative RT-PCR revealed that GAD67 was the major isoform of GAD in the salivary glands.