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PubMed1975

Histological changes in the submandibular glands of rats after intraductal injection of chemical carcinogens.

Carcinogens injected into the excretory canal of submandibular gland of Donryu rats revealed the following histologic changes in salivary glands. 20-Methylcholanthrene induced squamous cell metaplasia, fibrosis in the early stages, and "benign lymphoepithelial lesion"-like pattern after 3 months. Dense hyalinization occurred after 4-5 months with so-called "mixed tumor"-like pattern. In the later stages epidermoid carcinoma and fibrosarcoma were observed. 9, 10-Dimethylbenzanthracene caused degenerative change, metaplasia, fibrosis and cell infiltration, and later carcinoma and sarcoma appeared at a high rate. 4-Nitroquinoline-N-oxide led to dense hyalinization and so-called "mixed tumor"-like pattern was observed in many specimens. N-nitroso-N-methyl urethane and N-methyl-N-nitroso-N'-nitroguanidine revealed metaplastic changes, fibrosis and lymphoid infiltration. Scarlet red induced remarkable infiltration and aggregation of lymphoid cells, showing benign "lymphoepithelial lesion"-like pattern.

4-Nitroquinoline-1-oxide↗

PubMed1993

The B1-immunoreactive proteins of the perinatal submandibular gland: similarity to the major parotid gland protein, RPSP.

The B1-immunoreactive proteins of type III cells of the perinatal rat submandibular gland are immunologically cross-reactive with proteins of both the sublingual and parotid glands; in particular, protein SMG-A appears similar to a major parotid protein. We isolated SMG-A and the parotid protein (known as M1 or leucine-rich protein), prepared polyclonal antibodies to them, and compared their biochemical properties and immunological reactivities. They were identical in their molecular weight on SDS-PAGE (23.5 kDa), tenacious binding to Affi-gel Blue, isoelectric point (pH 4.53), and proteolysis to a 14 kDa peptide: Antibodies to SMG-A showed reactivity with protein SMG-C, a product of the neonatal type I cells, as well as with proteins SMG-B1 and SMG-B2, contrasted with the absence of reactivity of anti-M1 IgG with these proteins. Anti-M1 reacted with the "parotid secretory protein" (PSP) of the mouse, and M1 appears to be the homologue, in the rat, of mouse PSP.

Animals↗

PubMedDate not supplied

Immunohistochemical staining of human alpha-defensin-1 (HNP-1), in the submandibular glands of patients with oral carcinomas.

The purpose of this study was the immunohistochemical localization and distribution of HNP-1 in the submandibular glands of patients with oral carcinomas. Tissue sections were embedded in paraffin, and HNP-1 was immunostained by the streptavidin-biotin coupled peroxidase method. Striated duct cells in the submandibular glands were stained with anti-defensin antibody. Neutrophils and capillary intimal cells were also stained. Defensins (HNPs) are peptides that occur in neutrophils and protect against bacteria and tumor cells. Human alpha-defensin-1 (HNP-1) is such a peptide, possessing both antimicrobial and cytotoxic activities. The presence of HNP-1 in striated duct cells in the submandibular glands of oral cancer patients, suggests a likely role in tumor immunity, for this peptide.

Capillaries↗

PubMed1993

ATP4- increases the intracellular calcium concentration in rat submandibular glands.

1. The intracellular calcium concentration of a crude suspension from rat submandibular glands was increased by extracellular ATP. 2. The stimulatory effect of ATP was favored by removal of magnesium from the extracellular medium. ADP and adenosine had no effect. ATP did not modify the concentration of calcium in isolated rat pancreatic acini. 3. It is concluded that ATP is a potential neurotransmitter regulating the submandibular gland function.

Adenosine Triphosphate↗

PubMed2004

Age-related changes in IGF-1 expression in submandibular glands of senescence-accelerated mice.

Saliva is known to play important roles in such functions as swallowing, mastication, speech, and taste. Furthermore, salivary glands synthesize and secrete a number of growth factors involved in cell/tissue homeostasis. It has been demonstrated that IGF-1, which is structurally analogous to insulin, has been shown to be expressed in mouse submandibular glands, and that IGF-1 stimulates DNA synthesis, amino acid uptake, protein synthesis, and glucose transport in various cells. Diminished function of the salivary glands is thought to lead to increased dental caries and periodontal diseases, which are commonly associated with aging. However, very little is known regarding the effects of age on IGF-1 expression in submandibular glands. The senescence-accelerated mouse (SAM), an experimental murine model of accelerated aging, has been extensively used to examine the mechanisms responsible for aging. In the present study, IGF-1 production and mRNA levels in the submandibular glands of SAM-P1 mice were examined. IGF-1 levels were determined by radioimmunoassay and IGF-1 mRNA levels by semi-quantitative RT-PCR. We found that IGF-1 protein levels in homogenates and IGF-1 mRNA levels decreased with age in SAMP1 mice. These findings suggest that IGF-1 synthesis in submandibular glands decreases with aging, and this may result in lower levels of cellular proliferation, regeneration and wound healing in aged oral tissues.

Aging, Premature↗

PubMed1976

Stimulated growth of submandibular gland.

The effects of chronic isoproterenol (IPR) administration on the growth of submandibular gland were studied. Treatment of female rats with IPR, 0.02 mg. per gm. of body weight, twice daily between 13 and 29 days of age resulted in a 3.6-fold increase in the weight of the submandibular gland, with a 4-fold increase in ribonucleic acid and 1.8-fold increase in deoxyribonucleic acid content. Incorporation of tritiated thymidine was stimulated by two injections of the drug but it was below the control level after 5 days of IPR administration. When the administration of IPR was discontinued, the weight of the gland rapidly declined and within 11 days it reached the control level. However, the average deoxyribo-nucleic acid content of the glands of IPR-treated rats remained 20 to 25% above the control level. IPR treatment altered the cellular composition of the gland and influenced the proliferation of the various cell types differently. Between 14 and 30 days of age, the frequency of acinar cells increased from 29% to 44%. Concomitantly, the frequency of terminal tubule cells declined from 30% to 15%. There were no significant changes in the relative frequencies of other cell types during this developmental period. Chronic administration of IPR led to an increase in the frequency of acinar cells. At the same time the relative proportion of terminal tubule cells declined. During the observation period, the proliferative activities (labeling indices) of all cell types, except that of the ductal cells, declined. IPR treatment ahd the most pronounced, depressing effect on the proliferation of the acinar cells. At the same time, the drug accelerated the differentiation of acinar cells and it caused their marked hypertrophy. Administration of IPR to growing rats affords a favorable system for analysis of the relationship between normal and drug-induced growth.

Animals↗

PubMed1999

Expression of the cell-surface heparan sulfate proteoglycan mRNA in monkey submandibular gland.

We investigated the mRNA expression of cell-surface heparan sulfate proteoglycans, syndecans and glypican, in the adult female monkey submandibular gland using the reverse transcription-polymerase chain reaction (RT-PCR) technique. Agarose gel electrophoresis of the PCR products of the cDNA generated from RNA was carried out to demonstrate the expression of mRNA in syndecan-1, syndecan-2, syndecan-4 and glypican in this study. In order to compare the mRNA expression level among the cell-surface heparan sulfate proteoglycans, we measured changes in the relative intensity of PCR products with increasing thermal cycle number. The expression levels were syndecan-4 > syndecan-1, syndecan-2 > glypican. Considering these results together with our previous report, we found that the cell-surface heparan sulfate proteoglycans, syndecan-1, syndecan-2, syndecan-4 and glypican, are synthesized in the monkey submandibular glands, and that their ectodomains are released into the extracellular matrix. It was speculated that control of the expression patterns of the cell-surface proteoglycans may regulate the cellular function and behavior in the submandibular gland.

Animals↗

PubMed1991

Effects of castration and sex steroids on sexually dimorphic development of the mouse submandibular gland.

The aims of this study were to characterize sexual dimorphism in the submandibular glands of young adult mice and to determine how sex differences arise during postnatal development. In the mouse submandibular glands, prominent sexual dimorphism was observed at 30 days of age, when the male gland was superior in both the relative occupied area (ROA) and the mitotic rate of the granular convoluted tubules (GCT) to those of the female. By neonatal castration, this sexual dimorphism was abolished, and the intraglandular structures of castrated males were similar to those of normal females. In castrated mice of both sexes, daily treatment with testosterone and 5 alpha-dihydrotestosterone for 10 days from 20 days induced only the ROA of the GCT to increase to the normal male levels but not those of the other three regions of the glands, the acini, intercalated ducts and excretory striated ducts. Testosterone responsiveness of the glands, considering both the glandular weight gain and the mitotic rate of the GCT, was significantly higher in castrated males than in castrated females. On the other hand, 17 beta-estradiol had no effect on the glands of castrated mice. Therefore, the present study suggests that the testicular hormones are responsible for the masculine development of GCT of the glands, but not the ovarian hormones, and that there is a sex difference in the responsiveness of the glands to testosterone, which is more effective in males than in females.

Animals↗

PubMed1983

Induction of protein and glycoprotein synthesis in rat submandibular glands by isoproterenol.

A family of proline-rich proteins which contain over 40% proline and a glycoprotein were isolated from submandibular glands of isoproterenol-treated rats by extraction with 10% trichloroacetic acid and fractionation of the acid-soluble portion on Bio-Gel A-1.5m. The proline-rich proteins were subsequently separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Proteins were detected by formaldehyde fixation and Coomassie staining. After elution from the gels, amino acid compositions were determined. The family of proline-rich proteins (about six) appears to be qualitatively identical with a family of proteins from parotid glands of isoproterenol-treated rats (Muenzer J., Bildstein, C., Gleason, M., and Carlson, D. M. (1979) J. Biol. Chem. 254, 5623-5628, 5629-5634), except for a substantial change in the relative amount of each protein. An acid-soluble glycoprotein (GP-158) was not detected in extracts of submandibular glands of normal rats, but GP-158 was highly induced by isoproterenol treatment. This glycoprotein has an apparent Mr = 158,000 as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The major amino acids were Asx, 13%; Glx, 18%; Pro, 29% and Gly, 11%. GP-158 contained about 37% carbohydrate, and its sugar composition on a molar basis was mannose, 3.0; galactose, 2.1; N-acetylglucosamine, 3.5; fucose, 1.2; and sialic acid (N-glycolyl(4-O-acetyl)neuraminic acid), 0.9. N-Acetylgalactosamine was not detected. A glycopeptide isolated from GP-158 had the same sugar composition as GP-158. The amino acid sequence of the glycopeptide was shown to be Asp-Gly-(Asn)-Gln-Thr-Gln-Pro-Arg-Pro-(Gly-Pro). Only the parotid and submandibular glands of rats responded in this dramatic fashion to isoproterenol. The isoproterenol-treated rat is considered an appropriate model system for studying the overall effects of catecholamine beta-agonists on gene expression in these secretory tissues.

Amino Acid Sequence↗

PubMed1978

Morphometric and fine structural study of experimental autoallergic sialadenitis of rat submandibular glands.

To further our understanding of the immunopathologic mechanisms involved in experimental autoallergic sialadenitis of rat submandibular gland (EAS), histometric and fine structural studies were undertaken. Rats were immunized with allogeneic submandibular glands (SMG) emulsified in complete Freund's adjuvant. Control rats were not treated (C) or adjuvant treated (At). The rats were sacrificed 7, 14, 21 and 28 days after immunization and their SMG were processed for light and electron microscopy. Groups "C" and "at" showed normal acini and ducts. The SMG at 14 days showed significant loss of acini and granular ducts, severe lymphocytic infiltration and the appearance of undifferentiated ducts. The cells of the latter showed abundant free ribosomes, few profiles of rer, no secretory granules and in some cells autophagic vacuoles. Pseudopods of many lymphocytes were found in juxtaposition to degenerating parenchymal cells, mast cells and eosinophils. The extralobular ducts were significantly increased at 7, 14, and 21 days. The immunized glands showed evidence of regeneration at 21 and 28 days. Terminal tubule cells, proacinar cells and acinar cells, at various stages of maturation, were found in the regenerating glands.

Animals↗

PubMed1984

Salivary calculi and chronic sialoadenitis of the submandibular gland: a radiographic and histologic study.

This study correlated radiographic observations and histologic findings of submandibular glands with the diagnosis of salivary calculus and/or chronic sialoadenitis. During a 15-year period eighty-eight patients satisfied clinical requirements by having a radiographic examination performed prior to gland extirpation. Salivary calculi were present in 83% of the patients. The diagnostic accuracy of radiographs regarding salivary calculi in the submandibular gland system was 92%. Radiolucent calculi constituted 20% of the total number of cases with concrements. Failure to disclose concrements was caused by lack of contrast filling due to a damaged gland which presumably camouflaged radiolucent concretions. Ductal changes observed in sialograms corresponded to histologic changes in the glandular parenchyma in 96% of the cases. The absence of ductal change in sialograms did not necessarily indicate a nondiseased gland.

Adolescent↗

PubMed1983

Nerve-stimulated secretion of calcium by rat submandibular gland.

The comparative effects of electrical stimulation of parasympathetic (chorda tympani nerve) and sympathetic innervation to the rat submandibular gland on calcium secretion were examined. The separate roles of alpha- and beta-adrenergic receptors in the regulation of calcium secretion during sympathetic nerve stimulation were also determined. The present study shows that the parasympathetic and sympathetic innervations to rat submandibular gland have very different effects on [Ca] of saliva; the regulatory influence of the sympathetic is more prominent than that of the parasympathetic innervation; [Ca] of submandibular saliva evoked by chorda stimulation was about 25 times less than that of saliva evoked by sympathetic stimulation. However, since total volume of chorda-evoked submandibular saliva was about 20 times greater than that of sympathetically evoked saliva, the total output of calcium following stimulation of either autonomic branch was similar. Glandular depletion of calcium for both kinds of nerve stimulation was also similar. Comparison with previous studies on the rat parotid gland shows that the role of the parasympathetic innervation in regulation of [Ca] of saliva and glandular depletion of calcium differed in the two glands while that of the sympathetic innervation was generally similar for both submandibular and parotid glands. Calcium secretion from rat submandibular gland was decreased during sympathetic nerve stimulation in the presence of propranolol, a beta-adrenergic blocker, while it was greatly increased when the sympathetic nerve was stimulated in the presence of phentolamine, an alpha-adrenergic blocker. Thus, it was concluded that with both glands beta-adrenoceptors play the major role in the regulation of calcium secretion.

Animals↗

PubMed1999

Postnatal changes of gene expression for tissue inhibitors of metalloproteinase-1 and -2 and cystatins S and C, in rat submandibular gland demonstrated by quantitative reverse transcription-polymerase chain reaction.

The rat submandibular gland is not fully developed at birth and definitive differentiation takes place postnatally. The steady-state mRNA expression for the four proteinase inhibitor molecules, tissue inhibitors of metalloproteinase (TIMP)-1 and -2, and cystatins S and C, and for a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (G3PDH), in rat submandibular glands was measured by quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR) at different stages of postnatal development. The gene-expression patterns of TIMP-1 and -2 relative to G3PDH were similar to each other. The TIMP-2 and cystatin C genes were more highly expressed than those of TIMP-1 and cystatin S at all stages. Moreover, the gene expressions of TIMP-1 and -2, and of cystatins S and C, were predominant between 1 and 7, and 7 and 12 weeks of age, respectively, and coincided developmentally with the regression of terminal tubule cells and the differentiation of granular convoluted tubule cells, respectively. Quantitative competitive RT-PCR allowed accurate measurement of small changes in the steady-state concentrations of these proteinase-inhibitor mRNA molecules.

Animals↗

PubMed1986

Effect of advanced age on the induction by androgen or thyroid hormone of epidermal growth factor and epidermal growth factor mRNA in the submandibular glands of C57BL/6 male mice.

We have compared the responsiveness of the submandibular glands of mature (12 month old) and senescent (26-28 month old) male C57BL/6 mice to dihydrotestosterone (DHT) or triiodothyronine (T3) in terms of steady state levels of epidermal growth factor (EGF) protein and EGF mRNA. Northern blot analyses did not disclose any differences with age in the apparent sizes of EGF mRNA species. In untreated animals, submandibular glands of 26-28-month-old mice contained approximately 50% less EGF, and 75% less EGF mRNA than those of 12-month-old males. With advanced age, there was a 20% reduction in the absolute volume of the granular convoluted tubule (GCT) compartment, which is the exclusive site of EGF and EGF mRNA in the gland. In general, GCTs of old mice were composed of smaller cells with fewer secretion granules, but there was considerable cell-to-cell variation. In addition, there was greater variation in the intensity of immunocytochemical staining for EGF in senescent GCT cells, which also gave a lower and more variable in situ hybridization signal for EGF mRNA. After hormonal stimulation for 1 week with either tri-iodothyronine (T3) or dihydrotestosterone (DHT), EGF protein concentration in the glands was induced to the same level at both ages. However, EGF mRNA was 50% less abundant in old hormonally stimulated glands, compared to similarly treated young ones. Although many GCT cells in treated glands of senescent males respond to hormonal stimulation by increases in size and in content of secretion granules, there was cell-to-cell variation in responsiveness, especially after treatment with T3. These findings indicate that the decreases seen in the entire gland in EGF and EGF mRNA are caused by a wide-spread deterioration of the GCT cells themselves, which apparently can be reversed in many but not all GCT cells by stimulation with supraphysiologic doses of either T3 or DHT.

Aging↗

PubMed1983

Simultaneous computed tomography and sialography of the parotid and submandibular glands.

A technique of simultaneous computed tomography and sialography of the parotid and submandibular glands is described and the examination of 14 patients reported. Tumours were diagnosed in six cases and in the remaining eight cases inflammatory lesions were found. Sialographic enhancement offered definite advantages in localisation of lesions and examination of the tumour-normal tissue interface compared with either C.T. or sialography alone.

Humans↗

PubMed1994

Effects of vasoactive intestinal peptide and its homologues on the noradrenaline-mediated secretion of fluid and protein from the rat submandibular gland.

1. Noradrenaline-mediated secretion of fluid and protein from rat submandibular glands was enhanced by vasoactive intestinal peptide (VIP) and secretin but not by peptide histidine isoleucine (PHI) or gastric inhibitory peptide (GIP). 2. The synergistic effect of the combination of VIP with noradrenaline (NA) was antagonized by pretreatment with prazosin or phentolamine but not by pretreatment with yohimbine or propranolol. 3. These results suggest that VIP and secretin but not PHI and GIP can significantly enhance the secretion of fluid and protein that is mediated by NA in rat submandibular gland and that the synergistic effect of VIP and NA involves both alpha 1-adrenergic receptors and receptors for VIP.

Adrenergic Antagonists↗

PubMed1993

Polymorphous low-grade adenocarcinoma of submandibular gland origin.

A case of polymorphous low-grade adenocarcinoma (PLGA) in the submandibular gland is reported. A 72 year old woman presented with a 5 year history of a gradually expanding tumor in the submandibular region. The surgical specimen revealed a relatively well demarcated tumor, 35 x 35 x 20 mm in size. Macroscopically, necrosis and hemorrhage were not seen in the solid tumor. Histologically, the tumor growth pattern was variable, composed of tubular, papillary, solid, trabecular and cribriform structures. Immunohistochemically, some tumor cells were positive for epithelial membrane antigen (EMA), S-100 protein, keratin, and carcinoembryonic antigen (CEA). Electron microscopically, prominent microvilli projected into the luminal spaces, and basal lamina and hemidesmosomes were seen in the tumor cells adjacent to the connective tissues. The submandibular gland is an extremely rare location for PLGA. To the authors' knowledge, this is the first case of its kind reported in the English literature.

Adenocarcinoma↗

PubMed2000

Evidence for the AT1 subtype of the angiotensin II receptor in the rat submandibular gland.

We have characterized angiotensin II (Ang II) receptor subtypes on rat submandibular gland membranes using a radioligand binding assay. [3H]Ang II binding to the membrane fractions exhibited both high (Kd =0.08 nm, Bmax =2.19 fmol/mg protein) and low (Kd =4.19 nm, Bmax = 13.7 fmol/mg protein) affinity. Ang 11, Ang III and saralasin completely displaced the [3H]Ang II binding, whereas CV-11974, an AT1 receptor antagonist and PD123319, an AT2 receptor antagonist maximally displaced up to approximately 87 and 13% of the total binding, respectively. [3H]DuP753 binding to the membrane fractions exhibited a single population of binding site with a Kd of 4.22 nM and Bmax of 3.77 pmol/mg protein. Ang II, Ang III and CV-11974 completely displaced the [3H]DuP753 binding with slope factors near unity, but PD123319 did not. These findings suggest that rat submandibular gland membranes contain predominantly the AT1 receptor subtype.

Angiotensin Receptor Antagonists↗