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PubMed1982

The origin of substance P in the rat submandibular gland and its major duct.

The origin of the substance P-like immunoreactivity in the rat submandibular gland and its major duct was investigated. Lesions severing the sympathetic, pre- and postganglionic parasympathetic and sensory innervation of the submandibular gland, or treatment with the neurotoxin capsaicin produced only a small non-significant decrease in the substance P-like immunoreactivity content of the gland. In contrast both sensory denervation and capsaicin treatment produced a substantial decrease in the content of substance P-like immunoreactivity in the major duct of the submandibular gland. These observations indicate that the duct innervation is clearly of sensory origin, whilst the substance P-like immunoreactivity of the gland itself appears to be intrinsic.

Animals↗
PubMed1987

Differential effects of chronic reserpine exposure on Ca2+ sequestering mechanisms in rat submandibular gland vesicles.

To determine the effects of exposure to reserpine on subcellular Ca2+ transporting systems, active Ca2+ uptake was measured with and without ruthenium red in submandibular gland vesicles obtained from rats after chronic treatment with reserpine. The properties of ruthenium red-sensitive Ca2+ uptake were similar to those measured in submandibular gland vesicles from untreated rats: it was abolished by the dye, was relatively low at 1 microM Ca2+ but increased markedly at millimolar Ca2+ levels and was positively and significantly correlated with the mitochondrial membrane marker, cytochrome-C oxidase activity, in membrane subfractions obtained by differential centrifugation (r = 0.67, p = 0.0005, n = 29). On the other hand, ruthenium red-insensitive Ca2+ uptake, though stimulated at submicromolar Ca2+ concentrations, was reduced by a mean of 54% compared to preparations from untreated animals and particulate RNA content was 18% of that found in control preparations. Moreover, the distributions of ruthenium red-insensitive Ca2+ uptake and particulate RNA (which are closely correlated in vesicles from untreated rats) were not significantly related when measured in vesicles of submandibular glands from reserpine treated rats. Other membrane markers and overall membrane protein content were not significantly altered after chronic reserpine exposure. We conclude that reserpine treatment has little effect on mitochondrial Ca2+ uptake capacity but abolishes or drastically reduces the high affinity Ca2+-sequestering activity which, in submandibular gland vesicles from untreated rats, is apparently associated with the endoplasmic reticulum.

Animals↗
PubMed1985

Morphological and histochemical study of the submandibular gland in Praomys (Mastomys) natalensis.

The submandibular gland in female and male Praomys (Mastomys) natalensis (a South African multimammate rodent) was studied using light microscopy and techniques for the demonstration of carbohydrates. Hematoxylin and eosin stain revealed the presence of a single secreting component that gave a strongly positive PAS reaction. Limiting elements of the granular tubules gave a weakly positive PAS reaction. Acidic glycoproteins were evidenced only in granules of the acinar component.

Animals↗
PubMed1989

CGRP-immunoreactive sensory nerve fibers in the submandibular gland of the rat.

Indirect immunofluorescence technique was used to study the occurrence and distribution of CGRP immunoreactivity in the submandibular gland of normal rats and after unilateral sensory and sympathetic denervations. In normal rats, CGRP-immunoreactive nerve fibers and nerve trunks were seen around or in close contact with interlobular salivary ducts as well as around small blood vessels of the gland. Occasionally, CGRP-immunoreactive nerve fibers were also detected between or around the acini of the gland. The submandibular ganglia contained CGRP-immunoreactive nerve fibers, but the ganglion cells were not immunoreactive for CGRP. The trigeminal ganglion contained a population of CGRP-immunoreactive, mainly small sized ganglion cells and nerve fibers distributed throughout the ganglion. Unilateral electrocoagulation of the trigeminal nerve caused a significant reduction in the number of immunoreactive nerve fibers in the gland, although some fibers still were present in the ipsilateral glandular tissue. Unilateral superior cervical ganglionectomy caused no detectable effect on the number of CGRP-immunoreactive nerve fibers in the gland. The present results suggest that the rat submandibular gland contains CGRP-immunoreactive nerve fibers both around blood vessels and in glandular secretory elements. Denervation experiments support the view that the majority, but perhaps not all of them originate from the trigeminal ganglion.

Animals↗
PubMed1985

Sialographic damage in rat submandibular gland.

The damage caused to rat submandibular glands by intraductal injection was examined. When a small volume of isotonic saline was injected, even if salivation was not influenced, salivary composition was greatly affected because the intercellular junctions of the duct cells were damaged. Intraductal injections of hyperosmotic solutions or highly viscous liquids were more effective in damaging intercellular junctions. When interpreting the significance of a salivary composition in clinical diagnosis, it is necessary to consider the sialographic damage which might influence the salivary composition.

Animals↗
PubMed1985

Scanning electron microscopy of human submandibular gland.

The fracture surface of human submandibular gland analyzed by scanning electron microscopy is studied here. Acini showed spherical granules of 0.7 +/- 0.28 micron diameter, their most distinctive feature. Some empty, septate cavities found contiguous to serous acini were considered to be mucous acini. Striated ducts had a circular lumen, with microvilli forming prominences. Blebs, some intact and others ruptured, were interpreted as apocrine secretion. The 'separating zone' of the striated cells was distinguishable from the rest of the cell because the structure of the cell was granular whereas the 'separating zone' was fibrillar.

Adult↗
PubMed1994

The effect of removing external sodium upon the cholinergic regulation of potassium permeability in the rat submandibular gland in vitro.

Fragments of rat submandibular gland were loaded with 86Rb+ and superfused so that the rate of 86Rb(+)-efflux could be quantified as an indicator of potassium permeability. Acetylcholine evoked an increase in permeability consisting of a transient, calcium-independent response and a sustained, calcium-dependent. Total removal of external sodium significantly inhibited both phases of this response. The results thus confirm that the cholinergic regulation of potassium permeability is compromised by removal of external sodium but do not support the view that this is due, exclusively, to an effect on calcium influx.

Acetylcholine↗
PubMed2000

Subcellular localization of epidermal growth factor in human submandibular gland.

Epidermal growth factor in human submandibular gland was localized at the subcellular level by means of an immunogold staining method. Labelling was observed in serous acini and ducts. In the acini, gold particles were found within secretory granules, indicating that the growth factor is released into the saliva through granule exocytosis. In the ductal system, the most intense reactivity was revealed in the principal cells of striated ducts. In these cells, an abundant population of small cytoplasmic vesicles was specifically stained. Immunoreactive vesicles were found both apically and basally, suggesting that ductal cells can release their products not only into the saliva but also into the interstitium.

Adolescent↗
PubMed2004

Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction.

Nitric oxide is an intracellular and diffusible messenger of neurotransmitters involved in salivary secretion, as well as an inflammatory mediator in salivary gland diseases. It is synthesized by three different isoforms of nitric oxide synthase (NOS), each subject to a fine transcriptional, post-transcriptional and/or post-translational regulation. Our purpose was to study the possible mechanisms leading to NOS downregulation in submandibular glands of normal mice and in the nonobese diabetic (NOD) mouse model of salivary dysfunction with lower NOS activity. NOS activity and cGMP accumulation were determined by radioassays in submandibular glands of both mice in the presence of the protein kinase inhibitors KN-93 and bisindolylmaleimide. NOS I mRNA and protein expression and localization were assessed by RT-PCR, Western blot and immunohistochemistry. A downregulatory effect of calcium-calmodulin kinase II (CaMK II) on NOS activity in submandibular glands of both NOD and BALB/c mice was observed. Our results are consistent with a physiological regulation of NOS activity by this kinase but not by PKC in normal BALB/c mice. They are also supportive of a role for CaMK II in the lack of detectable NOS activity in submandibular glands of NOD mice. KN-93 also restored cGMP accumulation in NOD submandibular glands. The downregulation of NOS in NOD mice seems to be mainly mediated by this kinase rather than the result of a lower expression or different cellular localization of the enzyme. It was not related to different substrate or cofactors availability either.

Animals↗
PubMed2003

Blood flow and interstitial fluid pressure in the rat submandibular gland during changes in perfusion.

The submandibular gland is a cell-rich encapsulated organ with high transport of fluid through the interstitial space during salivation. We hypothesized that the gland is a low-compliant tissue, i.e., that a modest increase in fluid volume will produce a rise in interstitial fluid pressure (IFP) counteracting fluid filtration into the interstitium. To test this hypothesis, we measured IFP with micropipettes and glandular blood flow (GBF) with a laser-Doppler flowmeter during changes in perfusion. Clamping of the carotid artery or the jugular vein, or electrical stimulation of the sympathetic or parasympathetic nerve to the gland, induced changes in perfusion. Baseline IFP averaged 3.5 +/- 0.5 mm Hg. Clamping of the artery reduced IFP and GBF (-56.5 +/- 8.4% and -53.1 +/- 6.4%, respectively), whereas clamping of the vein decreased GBF (-21.6 +/- 14.3%) and increased IFP (141.2 +/- 27.4%). Sympathetic nerve stimulation reduced both parameters (-86.9 +/- 16.5% and -74.4 +/- 7.0%, respectively). In contrast, stimulation of the parasympathetic nerve elicited an increase in GBF (133.2 +/- 5.9%) and in IFP (173.3 +/- 41.4%). Thus, changes in vascular volume led to concomitant changes in IFP consistent with low tissue compliance, a phenomenon of importance for fluid volume regulation.

Animals↗
PubMed1984

Scanning electron microscopic and X-ray microdiffractometeric studies on sialolith-crystals in human submandibular glands.

The crystalline structures of 18 submandibular gland calculi were studied by radiomicrography , scanning electron microscope, and X-ray microdiffractometeric techniques. The following observations were made by SEM: Granular or globular structure was seen on the surface of all cases and pyramidal crystal in one case. In the inside, all showed lamellar pattern with amorphous nucleus in the center, and granular, plate-like and rhombohedral structures were also observed. X-ray microdiffractometeric analyses: Apatite was frequently observed in both outside and inside of the calculi. Whitlockite was next frequently detected and was seen more often in the inside. Brushite and weddellite were noted in the outside of calculi in one case each. Thus, it is suggested that brushite and weddellite were present in the front portion of calculus formation and then transformed into the more stable form e.g. apatite.

Apatites↗
PubMed2001

Sonographic detection of secondary MALT lymphoma of the submandibular gland.

This report describes a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the lacrimal glands that recurred in the submandibular salivary glands. Gray-scale sonography showed small hypoechoic nodules, measuring less than 0.5 cm in diameter, in both submandibular glands. The echogenicity and echotexture of the rest of the submandibular glands and of the parotid glands was normal. Power Doppler sonography revealed increased vascularity within the nodules. A sonographically guided aspiration biopsy of the nodules revealed MALT lymphoma. Secondary MALT lymphoma should be considered in the presence of multiple small hypoechoic nodules in the salivary glands in patients with a history of MALT lymphoma at another location.

Female↗
PubMed1992

Additive and/or synergistic effects of 5 alpha-dihydrotestosterone, dexamethasone, and triiodo-L-thyronine on induction of proteinases and epidermal growth factor in the submandibular gland of hypophysectomized mice.

The effects of androgen, glucocorticoid, and thyroid hormones on levels of proteinase isozymes and epidermal growth factor (EGF) in the submandibular glands of hypophysectomized (Hypox) mice were investigated. Total proteinase activity in males was decreased by hypophysectomy and increased by single or combined injection of the three hormones into these mice. 5 alpha-Dihydrotestosterone (DHT) had the strongest effect, and dexamethasone (Dex) the least. By isoelectric focusing, proteinases extracted from the submandibular gland of untreated male and female mice were fractionated into four isozymes with pI values of 4.8 (proteinase-F), 5.8 (proteinase-D), 6.2 (proteinase-A), and 10.0 (proteinase-P). In Hypox mice (both sexes), there was only a single isozyme, proteinase-F. Proteinase-D, -A, and -P were induced in the submandibular gland of Hypox males by injections of DHT, Dex, and/or T3; the percent ratio of activity of each of these isozymes induced by these hormones, given either singly or in combination, was almost parallel among the three isozymes. Synergistic effects were observed between T3 and Dex, and additive effects between T3 and DHT. The increase in proteinase isozyme activities by concomitant injections of T3 and Dex was about 2 times more than the additive values. The changes in proteinase-F upon hormone injection were complicated. In females, the enzyme activity was decreased by hypophysectomy and increased by DHT administration. In males, on the other hand, it was increased by hypophysectomy and suppressed by T3 or T3 plus steroid hormones. The EGF level in the submandibular gland was decreased to about 1/800th (males) or 1/90th (females) of its normal level by hypophysectomy. Its level in the Hypox animal was greatly increased by all three hormones, given singly or in combination. Synergism was also observed between T3 and steroid hormones; DHT plus T3 and T3 plus Dex induced EGF 6 times and 9 times, respectively, more than the additive values. These values were much greater than those for the induction of proteinase-D, -A, and -P by combined injections of T3 and steroids. The present results suggest that the genes coding for proteinase-A, -D, and -P are located close to each other and that the onset of their expression may be controlled by the same regulatory mechanism. By contrast, the gene for proteinase-F may be mapped to a different locus or regulated differently. The mechanism of induction of EGF by T3, DHT, and Dex appears to be similar to but not completely the same as that for proteinase-D, -A, and -P.

Animals↗
PubMed1980

Postnatal developmental changes in submandibular glands of rats and mice.

The submandibular glands of mice and rats are not fully developed at birth. In early postnatal life, differentiation of acini takes place before that of granular convoluted tubule (GCT) cells. The latter develop from striated duct cells, and first appear in both species around 15 days of age. In mice their full development gets under way by 20 days of age and is rapid in males and slow in females, resulting in a clear sexual dimorphism in adults. In rats, GCT development is more protracted, and accelerates around 40 days of age, with no sexual dimorphism seen at any time. The course of postnatal development of several GCT cell products is correlated with the cytodifferentiation of these cells. Reliable data are available for the development of amylase, proteases (including kallikrein), renin, epidermal growth factor, and nerve growth factor. Preliminary information exists for a glucagon-like substance. Cytodifferentiation of GCT cells is under hormonal control. Androgens alone can not precociously induce GCT cells, but thyroid hormones can do so, acting either alone or synergistically with androgens.

Amylases↗
PubMed1984

Two independently regulated secretory systems within the acini of the submandibular gland of the perinatal rat.

Rat submandibular glands undergo a transient stage of differentiation in the perinatal acini. Two morphologically distinct cell types (Type I and Type III) appear and secrete several electrophoretically identifiable proteins. To examine the regulation of the secretion of these proteins and their association with secretion by the two cell types, 4-day-old glands were incubated with secretory agonists and antagonists, and the cultures were evaluated for secreted proteins in the medium and morphologically assayed degranulation of the cells. Stimulation of glands with beta-adrenergic agonists resulted in the secretion of three proteins, A, B1, and B2, at Rf 0.26, 0.36, and 0.40 in native, anionic gels at pH 8.3. Cholinergic stimulation caused the appearance of a different protein, C, at Rf 0.12, but only slight secretion of A, B1, and B2. With both beta-adrenergic and cholinergic stimulation, another protein, D, was seen near the origin. Partial purification of the proteins was effected by gel chromatography followed by preparative IEF (Isoelectric point focusing). Proteins A, B1, and B2 were recovered at isoelectric pH 4.5, 5.4, and 5.1 respectively. SDS gels of IEF fractions and secretion medium indicate Mr 25K, 26K, 27K, 97K, and greater than 150K for A, B1, B2, C, and D respectively. beta-Adrenergic stimulation caused degranulation only of Type I cells and cholinergic stimulation only of Type III cells. We propose the existence of two independently regulated secretory systems in the perinatal acini, with Type I cells secreting protein C on stimulation of cholinergic receptors, and Type III cells secreting A, B1, and B2 through beta-adrenergic receptors. With either stimulation, protein D is secreted, and thus it may serve a general function in the secretion process.

Animals↗
PubMed1998

Significance of unilateral submandibular gland excision on salivary flow in noncancer patients.

OBJECTIVES/HYPOTHESIS: Normal salivary flow is important for maintaining good oral hygiene. Lack of normal flow predisposes to an increased incidence of dental caries and symptomatic xerostomia. The submandibular glands are responsible for 70% of resting salivary flow. Removal of the submandibular gland is most commonly performed for sialolithiasis, chronic sialoadenitis, or as part of a neck dissection. The effect of unilateral gland resection for benign disease on resting salivary flow has not been well examined in the literature. STUDY DESIGN: Case controlled study involving patients who had undergone a unilateral submandibular gland resection matched with normal control subjects. METHOD: Stimulated and unstimulated salivary flow rates in surgical and control subjects were measured in a controlled setting. RESULTS: Unstimulated salivary flow rates were 0.805 mL/min in the control group and 0.405 mL/min in the surgical group (P = .01). Stimulated salivary flow rates were not significantly different between the two groups (P > .05). Fifty-seven percent of patients in the surgical group and 14% in the control group had xerostomia (P < .05). CONCLUSION: Unilateral submandibular gland excision results in a decreased rate of resting salivary flow and an increase in subjective xerostomia.

Adult↗
PubMed1989

[Effects of cyproterone acetate on mouse submandibular gland].

It is recognized that the submandibular gland (SMG) of mice is one of the target organs for androgen, and a specific androgen-binding protein (androgen receptor) has been found in the cytosol fraction of this gland. Androgen participates in the production of histochemically and biochemically detected components of this gland through this receptor. Cyproterone acetate (CPA) is a synthetic progestogen which possesses antiandrogenic properties with some synandrogenic action. However, the action of CPA on the SMG has not been well defined. In the present study, the effects of CPA on the granular duct (GD) of the mouse SMG, which is the site of androgen action, were investigated using histometric, histochemical, and biochemical techniques. For histometric and histochemical experiments, normal adult male mice were treated with CPA (20, 40 and 80 mg/kg, S.C.) every second day for 5-30 days. In other experiments, castrated (CAS) and castrated-adrenalectomized (CA) mice were prepared, and they were given an injection of testosterone propionate (TP; 20 mg/kg, S.C.) and/or CPA (20 and 200 mg/kg, S.C.) every second day for 10 days. After the final administration, SMG weights were determined and the size of the GD in the SMG was measured by light microscopy using a micrometer. The sections of SMG were stained with methylgreen-pyronin, bromophenol blue, and p-dimethylaminobenzaldehyde in order to detect RNA (RNA staining), total protein (BPB staining), and granules (Try staining) in the GD, respectively. The intensity of each staining was measured by the method of Sato et al. For biochemical experiments, the mice with testicular feminization (Tfm), which are genetically deficient in androgen receptor, and genetically normal male (X/Y)-castrated mice were used. Both Tfm and X/Y-castrated mice were injected with CPA for histological experiments. After the administration period, the SMG's of both Tfm and X/Y-castrated mice were isolated and esteroprotease activity was determined by the method of Trautschold. The SMG of non-administered X/Y-castrated mice was homogenized in Tris-HCl buffer. And cytoplasmic extracts of SMG's from non-administered X/Y-castrated mice were prepared for detection of inhibitory effect of CPA on specific binding pattern of 3H-methyltrienolone (R1881) by the sucrose density gradient method.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

EGF-stimulated signaling by means of PI3K, PLCgamma1, and PKC isozymes regulates branching morphogenesis of the fetal mouse submandibular gland.

Branching morphogenesis of fetal mouse submandibular glands (SMGs) partly depends on the epidermal growth factor (EGF) receptor that triggers at least three intracellular signaling pathways involving (1) the mitogen-activated protein kinases ERK-1/2, (2) phospholipase Cgamma1 (PLCgamma1), and (3) phosphatidylinositol-3-kinase (PI3K). PLCgamma1 directly activates protein kinase C (PKC) isozymes; PI3K stimulates protein kinase B (PKB, also known as Akt), which ultimately activates PKCs and other proteins. We reported that the pattern of phosphorylation of ERK-1/2 in response to EGF in SMGs varies with fetal age and that blockade of EGF-stimulated ERK-1/2 signaling partially inhibits branching (Kashimata et al. [2000] Dev. Biol. 220:183-196). Here, we report on components of the PLCgamma1, PI3K, and PKC families of signaling molecules in fetal SMGs from the 13th day of gestation to postnatal ages. Western blotting revealed that (1) PLCgamma1 is present from E13 to E18 but drops off precipitously to negligible levels on the day of birth and thereafter, and (2) PI3K, PKB(Akt), and several PKC isozymes are expressed from E13 onward through adult life. Both PLCgamma1 and PI3K are phosphorylated in response to EGF. Inhibition of PI3K by LY294002 inhibited EGF-stimulated branching, but inhibition of PLCgamma1 by U73122 had no effect. Western blotting showed that the concentrations of 8 PKC isozymes vary with age in the fetal and postnatal SMG. However, general inhibition of PKCs by Calphostin C or specific inhibition of PKCalpha or of PKCepsilon by Gö6976 or Ro-32-0432, respectively, increased EGF-stimulated branching. Calphostin C also increased EGF-stimulated phosphorylation of ERK-1/2. These findings indicate that signaling from the EGF receptor in the fetal mouse SMG varies with development and triggers stimulatory effects by means of ERK-1/2 and PI3K but inhibitory effects by means of PKC isozymes.

Animals↗