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PubMed1994

Dephosphorylation of nuclear non-histone proteins in submandibular glands of rats treated with isoproterenol.

Protein phosphatase that removed [32P]phosphate from non-histone proteins, i.e., phenol-soluble acidic proteins, more rapidly and strongly than from histone proteins was present in nuclei of rat submandibular glands, but was not associated with chromatin. Cyclic AMP (10(-4)-10(-2) mM) stimulated the dephosphorylation of non-histone proteins, but not that of histone proteins. After a single injection of isoproterenol (IPR), the dephosphorylation of non-histone proteins in rat submandibular gland nuclei increased within 15 min, reached a maximum in 30 min and returned to normal control levels within 4 h. The stimulation of dephosphorylation of non-histone proteins induced by IPR was not observed after prior treatment of the animals with dichloroisoproterenol. The dephosphorylation of histone proteins was not affected by the injection of IPR. Stimulation of beta-adrenoceptors with IPR in rat submandibular glands resulted in increase in cyclic AMP and decrease in RNA synthesis in the tissues in the first few hours after the injection. This decrease in RNA synthesis was temporary and was preceded by the increase in cyclic AMP level and in the dephosphorylation of non-histone acidic proteins in the tissues. These results suggest that protein phosphatase in nuclei plays an important part in the events controlling RNA synthesis by regulating the state of phosphorylation of non-histone acidic proteins. In addition, the phosphatase may be regulated by a function of the cytoplasmic membranes.

Animals↗
PubMed2002

[Localization of senescence marker protein-30 (SMP30) in the mouse submandibular gland and histological findings in the SMP30 knock-out mouse].

Senescence marker protein-30 (SMP30), which has a molecular mass of 30 kDa, is strongly expressed during maturation and decreases with aging in the liver and kidney. SMP30 is suspected of being closely related to cell functions, especially intracellular Ca2+ homeostasis, in differentiated tissues of the liver and kidney. We produced an antibody against SMP30 to study the localization of SMP30 in the submandibular gland of normal mice using an enzyme-labeled antibody. The submandibular gland was also observed under transmission electron microscopy in newly created SMP30-knockout mice compared to normal mice. SMP30 was found to be widely distributed in acinic cells of ductal and peripheral areas of the submandibular gland. Degenerative mitochondria tended to be abundantly observed in cells with SMP30, although marked changes were not noted in SMP30-knockout mice.

Animals↗
PubMed1998

[Development of dipeptidyl peptidase IV (DPP IV) activity in postnatal differentiation of the submandibular gland in mice].

The localization of a serine exopeptidase--DPP IV--in the male and female submandibular gland of the mouse during gland postnatal development was studied histochemically in the light microscopic level. The present results suggest that localization of DPP IV is closely related to the postnatal differentiation and maturation of acini and male granular convoluted tubules. Remarkable sex differences of DPP IV activity were detected in the submandibular gland of pubescent and adult animals. The possible physiological role of DPP IV in major salivary glands is also discussed in the paper.

Aging↗
PubMed1986

Subcellular distribution of calmodulin and its binding proteins within the rat submandibular gland.

The involvement of calmodulin (CaM) in rat submandibular gland mucin secretion was investigated in vitro using a dispersed cell preparation. The CaM antagonist trifluoperazine (TFP) inhibited mucin secretion in response to both isoproterenol and dibutyryladenosine 3',5'-cyclic monophosphate. The inhibitory concentrations of TFP were between 10 and 100 microM. One millimolar TFP was toxic to submandibular cells and resulted in decreased levels of cellular ATP and a significant release of lactate dehydrogenase. Determination of CaM levels via radioimmunoassay within various subcellular fractions indicated that the majority of the CaM within the rat submandibular cell was located within the cytoplasm. CaM binding proteins were also identified within these subcellular fractions utilizing a gel overlay procedure. The two major, specific CaM binding proteins present within rat submandibular cells were a 59-kDa cytosolic protein and a 47-kDa membrane-associated protein.

Animals↗
PubMed1997

Prohormone convertases in mouse submandibular gland: co-localization of furin and nerve growth factor.

Nerve growth factor (NGF) in mouse submandibular glands (SGs) is generated from a 35-kD precursor by proteolytic enzymes that have yet to be identified. Prohormone convertases (PCs) cleave the NGF precursor in vitro, and in this study we questioned whether PCs could process salivary NGF in vivo. mRNA coding for PC2 (but not PC1) was detected on Northern blots of SG mRNA and also by in situ hybridization within parasympathetic neurons of intralobular ganglia. Northern blot and in situ hybridization analyses also detect mRNA coding for furin. In SGs of male mice, furin mRNA levels are high at birth and remain high throughout development. In glands from female mice, levels decline during postnatal development and are lower in adults than in newborns. Immunocytochemistry detects furin immunoreactivity in pro-acinar and ductal cells of glands from newborn and pubescent mice. In glands of adults, furin immunoreactivity is detectable in acinar cells but highest levels are present in NGF-containing granular convoluted tubule cells. These data, taken together with those from previous studies, suggest that furin is a candidate processing enzyme for NGF in mouse submandibular glands.

Animals↗
PubMed2002

H(1)-Receptor activation triggers the endogenous nitric oxide signalling system in the rat submandibular gland.

BACKGROUND: Histamine is released from mast cells by immunologic and non-immunologic stimuli during salivary gland inflammation, regulating salivary secretion. The receptor-secretory mechanism has not been studied in detail. AIMS: The studies reported were directed toward elucidating signal transduction/second messenger pathways within the rat submandibular gland associated with 2-thiazolylethylamine (ThEA)-induced H(1)-receptor responses. MATERIALS AND METHODS: To assess the H(1) receptor subtype expression in the rat submandibular gland, a radioligand binding assay was performed. The study also included inositolphosphates and cyclic GMP accumulation, protein kinase C and nitric oxide synthase activities, and amylase release. RESULTS: The histamine H(1) receptor subtype is expressed on the rat submandibular gland with high-affinity binding sites. The ThEA effect was associated with activation of phosphoinositide-specific phospholipase C, translocation of protein kinase C, stimulation of nitric oxide synthase activity and increased production of cyclic GMP. ThEA stimulation of nitric oxide synthase and cyclic GMP was blunted by agents able to interfere with calcium movilization, while a protein kinase C inhibitor was able to stimulate ThEA action. On the other hand, ThEA stimulation evoked amylase release via the H1 receptor but was not followed by the L-arginine/nitric oxide pathway activation. CONCLUSIONS: These results suggest that, apart from the effect of ThEA on amylase release, it also appears to be a vasoactive chemical mediator that triggers vasodilatation, modulating the course of inflammation.

Amylases↗
PubMed1989

Autonomic denervation effects on the kallikrein and striated duct cells of the rat and cat submandibular glands.

Chronic preganglionic parasympathetic denervation in the rat submandibular gland increases kallikrein activity whereas post ganglionic sympathetic denervation has no effect. Ultrastructural morphology of the striated duct following either denervation remains unaltered. Chronic preganglionic parasympathetic denervation in the cat gland dramatically reduces kallikrein activity and causes disruption and disappearance of subcellular organelles. Chronic sympathetic denervation has no effect.

Animals↗
PubMed1977

Electrophoretic isolation and partial characterization of a glycoprotein of the submandibular glands of the mouse.

A protein has been isolated from the water-extract of the submandibular glands of the mouse, after Biogel P-300 column passage, followed by preparative polyacrylamide gel electrophoresis at pH 4.3 and subsequently at pH 8.9, designated the AM1 protein. The isolated protein was electrophoretically pure in 7.5, 10 and 15% polyacrylamide gels both at pH 4.3 and at pH 8.9. Likewise, by electrophoresis in 15% sodium dodecyl sulfate-polyacrylamide gel only one protein band could be detected. Of the total amount of the water-extractable submandibular proteins the recovery of this protein component comprised 3 to 5 per cent. The molecular weight was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be 28 000, both in 7.5 and 15% gel. The isoelectric point was determined by isoelectric focusing in 4.8% polyacrylamide slabgel to be 4.85. The amino acid analysis showed that the ratio of acidic amino acids (Glx plus Asx) to basic amino acids (Lys plus Arg) is 2.3. The glycoprotein consists of protein for 77.4 per cent and of carbohydrate for 22.6 per cent. The molar ratio of the carbohydrates was GlcNH2:GalNH2:Man:Gal:Glc:Fuc:sialic acid = 22.0:1.3:3.0:1.7:10.0:2.6:0.3. The glycoprotein was not secreted from the submandibular glands by stimulation with cholinergic (acetylcholin) or adrenergic (noradrenalin) drugs both in vitro and in vivo. So, it appeared that this glycoprotein could be characterized as a cellular, non-secretory component of these salivary glands.

Amino Acids↗
PubMed1985

Correlation between Ca2+-stimulated adenosine triphosphatase activity and Ca2+ uptake in microsomal fraction of rat submandibular gland.

Both the Ca2+-ATPase activity and the Ca2+ uptake in a microsomal fraction of rat submandibular gland were inhibited by the addition of indomethacin in vitro. The decrease of both the Ca2+-ATPase activity and the Ca2+ uptake caused by the drug closely paralleled each other (r = 0.97). The inhibitory manner of indomethacin on Ca2+-ATPase and Ca2+ uptake was noncompetitive for Ca2+. These results suggest that the Ca2+-ATPase in the microsomal fraction of rat submandibular gland is a Ca2+ pump in this tissue.

Animals↗
PubMed1996

Cyclosporin A-induced functional and morphological changes in pilocarpine treated rat submandibular glands.

The effects of long-term administration of Cyclosporin A (CSA), an immunosuppressive agent, on submandibular glands of male albino rats were investigated. Sialochemistry studies revealed a reduction of pilocarpine-stimulated flow rates to 54% compared to the controls. Salivary Mg(2+) and K+ were elevated and a marked decrease in total protein concentration was observed. Light and electron microscopic features of treated glands show marked changes at tissue level. An irregular pattern of the nucleus, mitochondrial alterations, reduction in the number of secretory granules and their aggregation, disturbances of cytoplasmic organelles, and isometric vacuolation were among the most striking findings. Our results show that CSA causes marked functional and morphological alterations in rat submandibular glands, which may be due to the drug's direct effects on the tissue.

Animals↗
PubMed1977

Human submandibular gland tissue in culture I. Sulphate incorporation and tissue culture technique.

In vitro cultivation of human submandibular gland tissue resulted in release of salivary proteins corresponding to about 50% of the total content after 48 hours. The admixture of plasma proteins as judged by single radial immunodiffusion took place early in the incubation period, and could be reduced by discarding the first washing medium. Hydroxyproline measurements in the medium indicated that the autolysis increased significantly after two days of incubation. Isoelectric focusing of human submandibular proteins resulted in fractions with isoelectric points closely resembling those demonstraded earlier for monkey submandibular gland proteins, but with larger acid fractions and smaller basic fractions. Virus haemagglutination inhibition (HAI) activity and sulphate incorporation was demonstrated in the most acidic, viscous fractions, whereas L-leucine incorporation was found in all fractions of the isoelectric scale. No sulphate affinity to submandibular proteins, independant of the in vitro protein synthesis, could be detected by equilibrium dialysis or other control measures.

Adult↗
PubMed2004

A preliminary study of the submandibular gland of the rat after one-year cadmium intoxication. Part II. Pathomorphology and ultrastructure.

The aim of the present study was to establish to what degree a one-year exposure of rat females to 5, 50 and 100 mg of Cd/l affects cell morphology of the submandibular glands. After one-year cadmium exposure of female rats, at doses of 5, 50 and 100 mg Cd/l, a pathomorphological examination revealed periductal fibrosis in the submandibular glands of rats in all the three experimental groups, which increased with cadmium dose. We also found foamish cytoplasm in the cells of the submandibular glands in all the experimental groups, the intensity of that phenomenon also increasing with Cd dose. The ultrastructural examination revealed no abnormalities in Group I. However, in Groups II and III, we observed numerous granules with a secretion, varying in shape and size that filled up the cytoplasm both in the mucous and serous cells.

Animals↗
PubMed1976

[Influence of calcium and potassium ions on the parasympathetic stimulation secretory response of the isolated and perfused submandibular gland (author's transl)].

The effects of the submandibular gland perfusion with blood, Tyrode's solution, Tyrode's solution without calcium, and Tyrode's solution without potassium were studied. The effects on sodium, potassium, and calcium concentration in the saliva were studied in 11 dogs during electrical stimulation of the chorda tympani nerve. According to the statistical analysis we assume that: 1) the perfusion of the salivary gland with blood or Tyrode's solution does not alter sodium, potassium, and calcium concentration in the saliva; 2) the salivary perfusion with calcium free Tyrode's solution does not alter the chemical composition of the saliva; 3) the perfusion of the salivary gland with potassium free Tyrode's solution produce a decrease of the concentration of this ion in the saliva composition.

Animals↗
PubMed1982

Influence of thyroid hormone on (Na+ + K+)-dependent adenosine triphosphatase activity in rat submandibular glands.

Surgical thyroidectomy decreased (Na+ + K+)-dependent adenosine triphosphatase (Na-K-ATPase) activity in rat submandibular glands. Three successive doses of triiodothyronine (100 microgram/100 g of body wt) to euthyroid and hypothyroid rats produced 24 and 23 per cent increase in the enzyme activity, compared to control values. When hypothyroid rats were given smaller doses of triiodothyronine (4 microgram/100 g body wt every 48 h) for 27 days, Na-K-ATPase activity increased 40 per cent over the corresponding values in the control hypothyroid rats. Thus, thyroid hormone acts on rat submandibular glands to increase the Na-K-ATPase activity of that target tissue.

Animals↗
PubMed1975

Quantitative morphology and carbohydrate histochemistry of the mouse submandibular gland following prepubertal castration.

The endocrinologic basis for morphological and biochemical sex differences in the mouse submandibular gland have not been clarified. Previous studies have emphasized the maintenance of glandular differences in adult animals, rather than considering the factors responsible for their developmental etiology. Male CD-1 mice were castrated at intervals between 10 and 50 days of age and killed at 100 days. The quantitative development of granular tubules and the carbohydrate histochemistry of the submandibular glands were compared to untreated males and females. The area of granular tubules increased with age at castration. Nested analysis of variance indicated significant differences among treatments and among sections within individual glands. No group of castrated males had a greater development of tubules than untreated females. Carbohydrate histochemistry demonstrated an increase in carboxylated mucosubstances in the acinar cells and granular tubule cells of castrated animals.

Age Factors↗
PubMed2001

Daily changes in beta-adrenergic sensitivity of rat submandibular gland. Correlation with beta-adrenoceptor rhythm.

Neurons from the superior cervical ganglia (SCG) innervate the submandibular gland and release noradrenaline during the dark phase of the daily photoperiod. Since in the pineal, another structure innervated by sympathetic neurons, nocturnal activation of the SCG is associated with beta-adrenergic sub- and super-sensitivity rhythms, the possible existence of similar phenomena in the rat submandibular gland was assessed. Wistar female rats, kept on a 14:10 light/dark cycle (light from 06:00 to 20:00 h), were sacrificed at 09:00, 14:00, 20:00, 24:00 and 04:00 h. beta-Adrenoceptors were studied by 3H-dihydroalprenolol binding to membrane preparations. The equilibrium dissociation constant (Kd) did not change as a function of time while significant daily variations in maximal binding values (Bmax) were observed with a peak at 20:00 h. Changes in Bmax correlated with a high response of adenylate cyclase to isoproterenol. In addition, when the response in salivary flow to isoproterenol was measured. a shift to the left (about 1 logarithmic unit) in dose-response curves was observed at 19:00-20:00 has compared to 08:00-09:00 h. These daily variations in isoproterenol responsiveness seem not to depend on the pattern of eating since a 24-h starvation or a nocturnal starvation for 16-18 days did not abolish the morning-evening differences in the salivary flow response to isoproterenol. Rather, the results suggest that the daily variations in isoproterenol response correlate with beta-adrenergic super- and sub-sensitivity phenomena associated with the circadian release of noradrenaline from SCG neurons.

Adenylyl Cyclases↗
PubMed1986

Malignant schwannoma of the submandibular gland. A case report.

The first case of malignant schwannoma of the submandibular gland in a 23-year-old man with neurofibromatosis is reported. Light microscopy showed typical features of neurogenic sarcoma and an immunocytochemical study confirmed the schwannian differentiation of the neoplasm. The patient is still well without evidence of metastases or local recurrence of the tumor 80 months after the excision of the neoplasm.

Adult↗
PubMed1973

Spontaneous salivation in the rabbit submandibular gland.

1. Salivation has been studied in the submandibular gland of the rabbit. A very slow spontaneous salivation took place when all possibility of nerve influence had been excluded. Salivation was not due to ultrafiltration.2. The ;spontaneous' saliva had a mean K concentration of 148 mM and Na concentration of 46 mM. With increasing salivation rate produced by parasympathetic nerve stimulation, K concentration fell to a plateau level of about 30 mM whilst Na concentration fell rapidly to reach the low value of 3 mM, then began to rise again at the higher flow rates.3. Ligation of the submandibular duct produced a reversal of the ion concentrations in spontaneous saliva. By 4 days K concentration was lower and that of Na higher than control values until by 2 weeks the effect was maximal with mean concentrations of 25 mM for K and 153 mM for Na.4. Ouabain increased the spontaneous salivation rate and ethacrynic acid slowed or prevented it altogether. On the basis of the known sites of action of these drugs it is postulated that two pumps are involved in the regulation of spontaneous salivation. There appears to be basal activity of an acinar mechanism pumping NaCl into the lumen, taking water with it. This pump is activated directly or indirectly by the intracellular Na concentration which itself is controlled by an Na-K exchange pump.5. Excitation of the sympathetic trunk produced a small, though definite, increase in salivation rate. There was evidence that myoepithelial cells might also be involved in the sympathetic response and that they were activated by alpha receptor stimulation. Salivation evoked by sympathetic nerve stimulation would seem to be a response to beta receptor stimulation, but the possibility that activation of both alpha and beta receptors was required could not be excluded entirely.

Animals↗