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PubMed1989

Morphological changes in the submandibular gland of aging rats.

Age-related histological changes in submandibular glands of 5-, and 24-month-old Sprague-Dawley male rats were compared qualitatively using semi-thin sections of epoxy-embedded glands. Atrophy of acini and granular ducts with a concomitant hyperplasia of intercalated ducts were the dominant features seen in the 15- and 24-month-old glands compared to 5 months. In both aged groups (15 and 24 months) there appeared structures similar to terminal tubules normally seen during development. At 15 months irregular ducts consisting of a mixture of agranular cells and granular cells typical of granular ducts were found in continuity with the hyperplastic intercalated ducts. The significance of these age-related morphological changes remains speculative.

Aging↗
PubMedDate not supplied

The reserpinized rat in the study of cystic fibrosis: x-ray microanalysis of submandibular gland and pancreas.

The chronically reserpinized rat has been suggested as an animal model for cystic fibrosis. X-ray microanalysis of thick and thin cryosections was carried out to assess elemental redistribution in the submandibular glands and the pancreas of reserpinized rats at the cellular and subcellular level. In the submandibular gland of reserpinized rats, calcium and magnesium concentrations were significantly elevated. Mucus globules, secretory granules, and endoplasmic reticulum were the primary sites of the localization of excess calcium and magnesium. A significant potassium loss from the gland had occurred, particularly from the serous cells. Electron microscopy of conventionally prepared tissue showed marked swelling of the endoplasmic reticulum, especially in mucous cells. The elemental changes in the pancreatic acinar cells of reserpinized rats were reminiscent of elemental redistribution connected with cell death: increased levels of sodium, chlorine, and calcium and decreased levels of magnesium and potassium. Ultrastructural changes included swelling of the endoplasmic reticulum and obstruction of the acinar lumen. It is concluded tha elemental redistribution in chronically reserpinized rats presents interesting parallels with cystic fibrosis.

Animals↗
PubMed1986

Role of calcium and calmodulin in release of kallikrein and tonin from rat submandibular gland.

We investigated the role of calcium and calmodulin as intracellular mediators of kallikrein and tonin release induced by norepinephrine (NE). We studied the secretion rate of kallikrein and tonin from submandibular gland of rat in response to NE in the presence or absence of calcium, two calcium blockers, and four different calmodulin antagonists. Submandibular gland slices were incubated in vitro, and glandular kallikrein and tonin secreted into the incubation medium were determined by direct radioimmunoassays and expressed as nanograms per minute per milligram tissue. NE (10(-5) and 10(-4) M) increased the kallikrein secretion from the control value of 8.2 +/- 2.6 to 134.9 +/- 41.4 (P less than 0.05) and to 191.2 +/- 62.7 (P less than 0.05), and the release of tonin from a basal rate of 3.5 +/- 0.6 to 51.5 +/- 9.1 (P less than 0.05) and to 64.4 +/- 13.7 (P less than 0.05). The deletion of calcium and addition of EGTA into the incubation medium significantly attenuated the secretion of kallikrein and tonin induced by NE. Nifedipine, at concentrations which inhibit voltage-dependent calcium channels, did not affect the release of kallikrein and tonin, and only a high concentration (10(-4) M) reduced the release. TMB-8, a blocker of intracellular calcium, had no effect either. Phenothiazines, triflupromazine (10(-6) M) and trifluoperazine (10(-4) M), decreased significantly the kallikrein release elicited by 10(-5) M NE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

[Morphological study of lymphatic tissues after removal of the submandibular gland in the mouse (author's transl)].

In dd-mice of both sexes, the thymus, spleen and mesenteric lymph node were morphologically examined after the submandibular gland was extirpated at 35 days of age. When the bilaterally extirpated animals were fed with dried diet pellet which was commonly given to laboratory mice, the body weight decreased rapidly after operation and the thymus and spleen generally atrophied. The atrophy of the lymphatic tissues was especially marked in mice showing a fetal loss of body weight. In the lymphatic tissues, the cortex of the thymus, the follicular area and germinal center of the splenic white pulp, and the cortex of the mesenteric lymph node underwent remarkably atrophic changes. On the other hand, however, when the mice were fed after operation with a liquid diet made of commercial dry pellets, they grow gradually and the thymus, spleen and mesenteric lymph node were almost the same in weight and structure as those in controls. Very recently Martinez-Hernandez, Nakane and Pierce reported that removal of the submandibular gland from mice and rats was followed by loss of body weight and atrophy of the thymus and spleen, and that it caused selective depletion of lymphocytes from the thymus-dependent areas in the peripheral lymphatic tissue. These findings, however, could not be confirmed in the present study.

Animals↗
PubMed1989

A cytotoxic serine proteinase isolated from mouse submandibular gland.

We have isolated a novel cytotoxic factor from the submandibular glands of male BALB/c mice by Sephadex G-50 gel filtration chromatography and reverse-phase HPLC. The cytotoxic factor is a serine proteinase, which belongs to the mouse glandular kallikrein (mGK) family, with an Mr of approximately 27,000. The purified serine proteinase showed cytotoxic activity against mouse thymocytes in a dose-dependent manner, and a serine proteinase inhibitor, diisopropyl fluorophosphate, blocked its cytotoxic activity.

Animals↗
PubMedDate not supplied

Developmental changes of calcium-stimulated adenosine triphosphatase in rat submandibular gland.

Developmental changes in Ca2-+ ATPase activity were determined in submandibular glands of the rat from the fetus to the 300-day-old rat. Ca2+-ATPase in the homogenate fraction showed a rapid increase from the fetus to the 5-day-old rat, and from the 20- to 30-day-old rat. In the microsomal fraction, enzyme activity increased from the fetus to the 10-day-old rat, and after that is remained at almost the same level. Oscillatory phenomena of Ca2+-ATPase were observed in zymogen and mitochondrial fractions.

Adenosine Triphosphatases↗
PubMedDate not supplied

[Morphometric study of changes in the submandibular gland of aging rats. 2. Ducts].

A decrease in rat submandibular gland parenchyma could be observed with increasing age, consequent to an apparent increase in the proportion of intralobular ducts. Signs of acinar atrophy were noted with nuclei of smaller volume. A great variety of nuclear sizes and shapes was also observed. The blood vessels were smaller, and the connective tissue was increased. These histological data were confirmed in part by application of the technique of Chalkley. The granulous duct cell height is smaller in old animals.

Aging↗
PubMed2006

Immobilization stress induces BDNF in rat submandibular glands.

Brain-derived neurotrophic factor (BDNF) promotes survival and differentiation of the cells of the central and peripheral nervous systems. BDNF has been identified in non-neural tissue, including the heart, lung, platelets, lymphocytes, and lacrimal glands. Immobilization stress modifies BDNF mRNA expression in some organs. The present study examines the effect of immobilization stress on BDNF, and its receptor TrkB, in male rat submandibular glands. Increased BDNF mRNA and protein expression were observed in duct cells as a result of immobilization stress, as demonstrated by real-time PCR, Western blot, immunohistochemistry, and analysis by microdissection. TrkB mRNA was not detected in salivary gland tissue, or oral or esophageal mucosa, by RT-PCR. Rat submandibular gland was thus identified as an organ which expresses BDNF. Furthermore, the results of this study suggest that increased salivary BDNF expression occurs following immobilization stress.

Animals↗
PubMed1994

Carbachol-induced phosphatidylcholine hydrolysis and choline efflux in rat submandibular gland involves phospholipase D activation and is modulated by protein kinase C and calcium.

The role of calcium and protein kinase C activation in carbachol-induced choline efflux from submandibular glands was investigated. The participation of phospholipase D in this signal transduction pathway was demonstrated by the formation of [14C]phosphatidylethanol in [14C]lysophosphatidylcholine-labelled submandibular gland cells treated with carbachol or noradrenaline in the presence of ethanol. Chelation of the intracellular calcium with BAPTA/AM reduced the carbachol stimulated outflow of [3H]choline. The calcium ionophore A23187 in a high concentration (10 microM) increased the basal [3H]choline outflow, but decreased the carbachol-induced outflow. Removal of the extracellular calcium enhanced the carbachol-stimulated outflow, which returned to control when calcium was re-added to the medium. Activation of protein kinase C by phorbol-12,13-dibutyrate (100 nM) or 1-oleyl-2-acetyl-sn-glycerol (20 microM) was without effect per se, but enhanced the carbachol-mediated outflow of [3H]choline. Phorbol-12,13-dibutyrate in combination with 1 microM A23187 induced a small efflux of [3H]choline. A 2 h treatment with phorbol-12,13-dibutyrate (1 microM), causing down-regulation of protein kinase C, significantly decreased the carbachol-stimulated [3H]choline outflow. In conclusion, elevation of intracellular calcium levels and protein kinase C activation are of importance for the carbachol-stimulated outflow of [3H]choline. Inflow of calcium, if anything, reduces the carbachol-stimulated outflow of [3H]choline. Since phosphatidylcholine breakdown generates diacylglycerol and this could lead to activation of protein kinase C, activation of this signal transduction pathway may be important for the protein content of the saliva and for the known trophic effects of parasympathetic innervation.

Animals↗
PubMed1997

A method to estimate the transient interstitial osmolarity change upon application of osmotic stress in perfused rat submandibular gland.

Transient osmolarity changes in the interstitium of perfused rat submandibular glands were estimated by measurement of the interstitial Cl- concentration ([Cl-]ECF) with an Ag-AgCl electrode upon application of osmotic stress by the addition or subtraction of NaCl. A simple model was used to describe the interstitial osmolarity changes upon the application of osmotic stress. The measured [Cl-]ECF values and interstitial osmolarities were fit well by an exponential function derived from the model. The good fit of the theoretical curve indicates that this model describes adequately the changes in interstitial osmolarity after switching the perfusate osmolarity to a new value.

Animals↗
PubMed1986

Age-related changes of rat submandibular gland: a morphometric and ultrastructural study.

Age changes of the submandibular glands (SMG) of male rats were studied morphometrically and ultrastructurally from youth to old age. The most conspicuous feature of the aged SMG was regressive changes of the granular ducts. The extent and height of the granular ducts decreased as well as the content of mature secretory granules. These changes may play an important role for an individual rat, because the granular duct synthesizes many biological factors. Cytoplasmic crystalloids, salivary deposits and oncocytic transformation were also found in the SMG of rats more than 22-months-old. It was noticeable that the intercalated duct cells were especially affected by both crystalloid formation and oncocytic transformation.

Aging↗
PubMed1986

Changes in histological features and nerve growth factor content of the submandibular gland in the genetically obese (ob/ob) mouse.

Changes in the submandibular glands were studied cytologically in the genetically obese (ob/ob) mouse. In the ob/ob mice, the acini of the glands were mainly composed of mucous cells; in contrast to an abundance of serous cells in the lean controls. The convoluted tubular portions of the glands of the obese mice were composed of cells with reduced numbers of granules, as compared with the controls. The immunocytochemical reactivity to an antiserum against nerve growth factor (NGF) was mostly restricted to the convoluted tubular cells and tubular lumen in both male and female control mice. In the male and female obese mice, weak reactivity to NGF was found in the convoluted tubular cells, while none was observed in the tubular lumen. The reactivity to anti-NGF was lower in females than in males in both the obese and control mice. These changes may be related to the hypoactivity of the sympathetic nervous system in the obese mouse.

Animals↗
PubMed2000

Reversible regulation of P2Y(2) nucleotide receptor expression in the duct-ligated rat submandibular gland.

Ligation of the main excretory duct of the rat submandibular gland (SMG) produces a pronounced atrophy that is reversed upon ligature removal. Based on previous studies by our group and others suggesting that P2Y(2) nucleotide receptors are upregulated in response to tissue damage, we hypothesized that P2Y(2) receptor activity and mRNA levels would increase after duct ligation and return to control levels after ligature removal. Our results support this hypothesis. Intracellular Ca(2+) mobilization in response to the P2Y(2) receptor agonist UTP in SMG cells was increased significantly after ligation periods of 1.5 to 7 days, whereas no significant response was observed in the contralateral, nonligated gland. P2Y(2) receptor mRNA, as measured by semiquantitative RT-PCR, increased about 15-fold after 3 days of ligation. These increases reverted to control levels by 14 days after ligature removal. In situ hybridization revealed that the changes in P2Y(2) receptor mRNA abundance occurred mostly in acinar cells, which also were more adversely affected by ligation, including an increase in the appearance of apoptotic bodies. These findings support the idea that P2Y(2) receptor upregulation may be an important component of the response to injury in SMG and that recovery of normal physiological function may signal a decreased requirement for P2Y(2) receptors.

Animals↗
PubMed2001

Phosphodiesterase 3 as a potential target for therapy of malignant tumors in the submandibular gland.

Phosphodiesterase (PDE) 3s have been characterized in human neoplastic submandibular gland intercalated duct HSG cells. There have been no reports on PDE3 in malignant salivary gland cells. PDE3 activity was detected in homogenates of HSG cells. About 75% of PDE3 activity in HSG cells was recovered in supernatant fractions and 25% in particulate fractions. PDE3A and 3B mRNAs were detected by reverse transcription-polymerase chain reaction in RNA from HSG cells. The nucleotide sequences of the fragments were identical to those of human PDE3A and 3B. The PDE3-specific inhibitor, cilostamide, inhibited the growth of HSG cells. Our results indicate that PDE3s may be important in the growth of HSG cells. PDE3 thus appears to be a potential new target for antiproliferative therapies.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Basic isozymes of chymotrypsin-like esteroprotease from the mouse submandibular gland.

Basic isozymes of chymotrypsin-like esteroprotease from mouse submandibular glands were purified 60-80-fold by a rather simple procedure consisting of CM-Sepharose CL6B chromatography and gel filtration on Sephadex G-100. The purified sample contained three major isozymes (A, B, C) and some minor ones. Their isoelectric points were between pH 10 and 11. The molecular weights of the main isozymes were estimated at 28000 by SDS-polyacrylamide gel electrophoresis. The acidic isozyme (A) separated into two polypeptide chains whose molecular weights were 21500 and 6500. Specific activities of these isozymes using Bz-Tyr-OEt as substrate were comparable to that of bovine pancreatic alpha-chymotrypsin, but they hydrolyzed casein 10 times slower than did alpha-chymotrypsin. The hydrolytic activities of these isozymes on Bz-Tyr-OEt were inhibited by diisopropylfluorophosphate, tosyl-L-phenylalanine chloromethyl ketone and chymostatin, but they were 400 times less sensitive to chymostatin than was alpha-chymotrypsin.

Animals↗
PubMed2002

[Metastasis in submandibular gland from a leiomyosarcoma of the uterus].

Two general types of metastases should be distinguished in metastatic salivary gland tumors: one of them are tumors originating in the head and neck region, and the other are tumors from distant tumor sites. Distant metastasis affecting the submandibular gland are a rare entity. We report a case of the uterus leiomyosarcoma which metastatised in the submandibular gland.

Female↗
PubMed1990

Carcinosarcoma of the submandibular gland. An autopsy case.

We present a rare case of submandibular gland carcinosarcoma occurring in a 45-year-old male patient. His clinical history revealed that the carcinosarcoma had developed from a carcinoma ex mixed tumor in three years. In spite of repeated resection, intensive chemotherapy and irradiation, the tumor recurred and grew rapidly, and the patient died of hemothorax caused by rupture of a pulmonary metastatic tumor. The fourth recurrent tumor and autopsy specimens showed features of carcinosarcoma consisting of three tumor components, i.e., undifferentiated carcinoma, and chondrosarcomatous and osteosarcomatous growth. The metastatic nodules in both lungs and pulmonary hilar lymph nodes showed the same pattern. Immunohistochemically, the chondrosarcomatous cells were positive for vimentin and S-100 protein, and for epithelial markers such as epithelial membrane antigen (EMA) and cytokeratin (MA-902). Undifferentiated carcinoma cells, on the other hand, were partially positive for muscle actin other than cytokeratin (KL 1). Ultrastructurally, desmosome-like structures were seen in the chondrosarcomatous cells. These findings suggest that the sarcomatous lesions might have originated from epithelial cells.

Actins↗
PubMed1986

Ultrastructure of the submandibular gland in the rabbit.

The secretory endpieces of the rabbit submandibular gland are unusual in that they consist of seromucous acini (not demilunes) that empty into serous tubules that in turn drain into intercalated ducts. Seromucous granules consist of a moderately dense spherule in a fibrillogranular matrix. Serous granules contain a feltwork of filaments, which are liberated as a tangled skein during exocytosis. Peculiar granulated cells that have secretory granules of complex morphology are present at each end of the serous tubules. Intercalated ducts are, cytologically speaking, relatively simple, but the duct cells may contain a few oblong secretory granules. Striated ducts are typical in structure, although postfixation with ferrocyanide-reduced osmium reveals significant amounts of glycogen in the basal processes. Modified mitochondria are present in striated duct cells, but their frequency varies from rabbit to rabbit. Such mitochondria contain either an array of parallel, rigid cristae linked by intermembranous bridges, or a bundle of helical filaments within an expanded crista. Interspersed with the striated duct cells, especially near the duct origin, are some highly vacuolated cells with sparse mitochondria. Excretory ducts consisting of stratified columnar (sometimes pseudostratified) epithelium often show bleb formation of the luminal surface of the tall cells.

Animals↗