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At least 1,261 records · Page 70Linked to original sources
PubMed2002

Developmental and androgenic regulation of the immunocytochemical distribution of mK1, a true tissue kallikrein, in the granular convoluted tubule of the mouse submandibular gland.

The action of androgens on the immunocytochemical distribution of mK1, a true tissue kallikrein, was examined in the submandibular gland (SMG) of developing and adult mice by indirect enzyme-labeled and immunogold-labeled antibody methods for light and electron microscopy, respectively. In both sexes at 3 weeks of age, essentially all of the immature granular convoluted tubule (GCT) cells were uniformly immunostained. At 4 weeks of age (the onset of puberty), morphological differences between the two sexes appeared in the GCTs, in which some cells became immunonegative. Thereafter, the immunonegative GCT cells became more abundant in the SMG of males than of females and considerable intercellular variation in staining intensity for mK1 was seen, especially in males. A few slender GCT cells with strong immunoreactivity appeared in GCT segments only in males. Castration of males resulted in an increase in the number of immunopositive GCT cells, whereas administration of dihydrotestosterone (DHT) decreased the number of immunopositive GCT cells in the SMGs of both sexes. Slender GCT cells immunoreactive for mK1 were seen in females treated with DHT for 6 days. However, there were no immunostained slender GCT cells in female SMGs after injection of DHT for 2 weeks. Immunoelectron microscopy disclosed this type of cell in male SMGs, which closely resembles immature GCT cells of prepubertal mice, with a few small secretory granules uniformly labeled with gold particles, a sparse Golgi apparatus and RER, and basal infoldings. In mature male SMGs and in SMGs of DHT-treated females and castrated males, typical GCT cells had a well-developed Golgi apparatus and a net-like RER but few to no basal infoldings, whereas in the female gland equivalent cells had moderately developed RER and some basal infoldings. These results suggest that mK1 is one of the enzymes characteristically present in immature GCT cells and that its synthesis is inhibited in part by androgens, resulting in decreased numbers of immunopositive cells.

Aging↗
PubMed1995

On the relation of calcium channel blockers to rat parotid and submandibular glands function in vivo.

1. The effects of nifedipine, verapamil and diltiazem on rat parotid and submandibular glands function were studied. 2. Nifedipine (5 mg/kg), verapamil (5 mg/kg) and diltiazem (10 mg/kg) were injected intraperitoneally 15 min before saliva collection. 3. Animals were anesthetized with 50 mg/kg of sodium pentobarbital and 8 mg/kg of pilocarpine was used as secretagogue. 4. Submandibular saliva was analyzed for flow rate, protein and calcium concentrations; and parotid saliva for calcium and amylase contents. 5. In treated groups, flow rate and calcium of submandibular saliva were significantly lower than controls. Parotid calcium in the nifedipine group was decreased and in verapamil and diltiazem groups was increased. Parotid amylase was significantly decreased in both the nifedipine and diltiazem groups. 6. It is concluded that a blockade of calcium channels in salivary glands acinar cells by CCBs causes some alterations in salivary secretions.

Amylases↗
PubMed1999

[Sarcoidosis presenting as isolated nodules of the parotid and submandibular glands].

The authors documented the case of healthy, 50 year old women with a sarcoid lesions of the parotid and submandibular gland without any other manifestations of the disease. The presence of noncaseating granulomas in salivary tissue is a specific feature of sarcoidosis. Primary involvement of the intraglandular lymph nodes with a secondary involvement of the salivary gland parenchyma was detected. Etiopathogenesis, diagnostics and clinical features of sarcoidosis were presented.

Diagnosis, Differential↗
PubMed1981

Effects of chronic reserpine administration on beta adrenergic receptors, adenylate cyclase and phosphodiesterase of the rat submandibular gland.

Chronic administration of reserpine to rats resulted in a doubling of the density of beta adrenergic receptors in submandibular gland membranes as determined by [3H]dihydroalprenolol binding. The affinity of the labelled drug for the receptor were not altered. There was a concomitant increase in the isoproterenol-stimulated cyclic AMP levels in slices of the gland when incubated in the absence of a phosphodiesterase inhibitor. However, this increase in cyclic AMP accumulation appears to be related to a decrease in phosphodiesterase activity rather than to the increase in the density of beta receptors, since glands from control and reserpinized animals accumulated equal amounts of cyclic AMP when incubated in the presence of a phosphodiesterase inhibitor. In addition, there was no difference between glands from controls and reserpine-treated rats in catecholamine-stimulated adenylate cyclase activity, but the Vmax of the phosphodiesterase was decreased 36% in glands from the treated animals. Similar results were obtained when control and surgically denervated glands were compared. The increase in beta adrenergic receptors appears to be the result of the depletion of norepinephrine due to reserpine administration, whereas the decreased phosphodiesterase activity may result from decreased cyclic AMP levels, secondary to the decrease in norepinephrine.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1980

[Role of grafted Schwann cells in the regeneration of intraspinal nerve fibers when peripheral nerve, skeletal muscle or submandibular gland fragments are transplanted into the spinal cord of the mouse].

Small pieces of peripheral nerve, skeletal muscle or submandibular gland, taken from young or new-born mice, were grafted into the non-transected spinal cord of young albino mice, at the thoracic level, through a punctiform meningeal opening. Neighbouring intraspinal nerve fibres, severed during the grafting process, regenerate into and eventually throughout the transplants. In this regenerative process, sedentary or migrating Schwann cells of the transplants probably have a prominent influence in guiding the growth of the axonal sprouts they ensheathe and eventually myelinate.

Animals↗
PubMed1990

Significance of 5 alpha-androstane-3 alpha, 17 beta-diol in submandibular gland.

5 alpha-Androstane-3 alpha, 17 beta-diol (3 alpha-diol) was measured in the submandibular gland (SMG) of male and female rats by radioimmunoassay (RIA) at 4 and 7 weeks of age. The raised and constant concentration of 3 alpha-diol was revealed in female SMG. The mean values of 3 alpha-diol in female SMG were found to be significantly higher than testosterone (T) and dihydrotestosterone (DHT). 3 alpha-diol in male SMG was similar to that of DHT and these two steroids decreased by the 7th week.

Androstane-3,17-diol↗
PubMed1985

Effect of phospholipase A2 on Ca2+-stimulated adenosine triphosphatase activity in microsomal fraction of rat submandibular gland.

The effect of phospholipase A2 on the Ca2+-ATPase (EC 3.6.1.3) activity in the microsomal fraction of rat submandibular gland was kinetically studied in vitro. The Ca2+-ATPase activity was significantly increased by the treatment with phospholipase A2 in the presence of bovine serum albumin as a scavenger for hydrolyzed products. When the microsomal fraction was incubated with phospholipase A2 in the absence of bovine serum albumin, the Ca2+-ATPase activity was not altered. The Vmax and Km values for both ATP and Ca2+ were increased by the phospholipase A2 treatment, respectively. These results indicated that the activation of Ca2+-ATPase by the phospholipase A2 treatment is due to the increase of Vmax.

Animals↗
PubMed1988

Effect of androgen and thyroid hormones on renin-1 messenger ribonucleic acid levels in mouse submandibular gland.

The synthesis of renin and other biologically active polypeptides in the granular convoluted tubule cells of the mouse submandibular gland (SMG) is regulated by androgen and thyroid hormones. In this study genetically hypothyroid (hyt/hyt) mice carrying a single renin structural gene (Ren-1) were used to investigate the mechanism of hormonal action in mouse SMG. Treatment of female mice with 5 alpha-dihydrotestosterone (DHT) and/or thyroxine (T4) enhanced renin-1 activity and increased renin-1 mRNA, determined by Northern analysis. Compared to euthyroid (hyt/+) littermates, hyt/hyt mice had lower basal levels of renin-1 mRNA and a blunted response to either hormone alone. DHT and T4 acted synergistically to increase renin-1 activity and renin-1 mRNA in the SMG of hyt/hyt females. Furthermore, levels of renin-1 activity and renin-1 mRNA varied concordantly in the SMG of these animals. These data indicate that androgen and thyroid hormones influence levels of renin-1 in mouse SMG primarily by regulating the amount of renin-1 mRNA available for translation.

Animals↗
PubMed1995

Differential expression of transforming growth factor-alpha and epidermal growth factor during postnatal development of rat submandibular gland.

The concentration and the localization of transforming growth factor (TGF)-alpha and epidermal growth factor (EGF) in the submandibular glands (SMGs) of male Wistar rats of different ages (postnatal 0 to 10 weeks of age) were examined. Highest levels of TGF-alpha were seen early, at postnatal day 0; the levels dropped thereafter in an age-dependent manner, while EGF was not detectable before the third postnatal week. Immunoreactive localization of EGF was restricted to the granules of the granular convoluted tubule (GCT) cells in the mature SMGs, whereas TGF-alpha was observed throughout postnatal development over the entire duct system. TGF-alpha was demonstrated in the cytoplasm at early stages when the GCT granules were not observed and was also located on the granules at the late stage, as was the case for EGF, indicating that TGF-alpha is colocated with EGF in the mature SMG. These results demonstrate the differences between the expression of TGF-alpha and that of EGF in the developing rat SMG.

Age Factors↗
PubMed2004

Expression patterns of claudin family of tight junction membrane proteins in developing mouse submandibular gland.

Here, we investigated the expression of the claudin family of tight junction transmembrane proteins in the developing mouse submandibular gland. Data obtained by reverse transcriptase-polymerase chain reaction, Western blot, and immunofluorescence microscopy showed the expression and localization of claudin-3 to -8, -10, and -11 at epithelial tight junctions. Examination of the glands taken from embryonic day (E) 14, E16, and newborn mice revealed differential expression patterns of these claudins in the developing epithelium. Claudin-3, -5, and -7 were expressed in all of the luminal epithelial cells of the ducts at all of the developmental stages examined and in those of terminal tubules at E16 and later. Claudin-4 was expressed mainly in the ducts at all the developmental stages. The expression of claudin-6 and -8 was also restricted to the ducts at E14 and E16; but after birth, the former was undetectable, whereas the latter was expressed in both the ducts and terminal tubules. Claudin-10 and -11 were detectable mainly in the terminal tubules at E16 and later. In addition to being found in the epithelium, claudin-5 was also expressed in certain mesenchymal cells, probably endothelial cells. These results will provide a valuable resource for further investigation of tubulogenesis and physiological regulation of claudin-based tight junctions.

Animals↗
PubMed1987

Electron microscopic immunostaining of nerve growth factor: secretagogue stimulated submandibular glands.

Immunocytochemical localization of nerve growth factor (NGF) was assessed on thin sections of plastic-embedded male mouse submandibular glands by electron microscopy. Both control and secretagogue-stimulated glands were examined. NGF was localized in granules of both granular convoluted tubule (GCT) cells and transition cells. The latter were intermediate in morphology between GCT cells and striated duct cells. Both large and small granules were immunostained in GCT cells; however, considerable variability in immunostaining intensity was observed in both sizes of granules but especially in the small granules of transition cells. Rough endoplasmic reticulum (RER) in both cell types exhibited NGF immunoreactivity. No Golgi-associated immunostaining was observed. Following alpha-adrenergic stimulation with phenylephrine, NGF-containing granules were sharply reduced because of extensive degranulation. Pools of immunostained secretory material suggested intracellular fusion of NGF-containing granules. Immunostaining was also observed on membrane fragments found within large vacuoles in GCT cells. Evidence of NGF secretion after beta-adrenergic or cholinergic stimulation was less dramatic. In isoproterenol-stimulated GCT cells there was evidence of fusion of small, apical, NGF-stained granules. These cells also possessed heavily immunostained apical membrane blebs. Pilocarpine-stimulated cells exhibited pleomorphic immunostained apical granules but less apical membrane immunostaining. Abundant basal lysosomes appearing in GCT cells after pilocarpine stimulation did not stain for NGF.

Animals↗
PubMed2002

Divergent expression and localization of aquaporin 5, an exocrine-type water channel, in the submandibular gland of Sprague-Dawley rats.

By Western blot analysis, the expression level of aquaporin (AQP) 5 in the submandibular gland (SMG) was found to be different among individual rats of the Sprague-Dawley (SD) strain. Such differences were observed for AQP5 but not for AQP1 and consequently the SD strain was divided into two groups, one expressing a high level of AQP5 and the other a low one. The difference in average intensity of expression between the two groups was more than twofold. Immunohistochemical analysis of the SMG demonstrated that the AQP5 protein was localized in the basal and apical/lateral plasma membrane of acinar cells in rats expressing the high level of AQP5. In the rat expressing the low level, however, this channel protein was localized strongly in the apical/lateral plasma membrane, but only very weakly in the basal membrane of the acinar cells. Such a diverse localization of AQP5 was confirmed by Western blotting as well. Breeding between brother and sister was repeated for two times within high expressers and low expressers to obtain the third generation progenies (F2); the AQP5 level of the SMG in the third generation (F2 rats) from high expressers was significantly higher than the F2 from low expressers. Our present study suggests the existence of genetic variation in the expression of a water channel protein, AQP5, in rats.

Animals↗
PubMed1990

Evidence of transformed androgen receptor in rat submandibular gland by three-step column chromatography.

The transformation of cytosolic androgen receptors was studied in the male rat submandibular gland (SMG) at 3 and 7 weeks of age, using 3H-R1881 as the labeled ligand. Sephacryl S-200 column chromatography revealed two R1881 binding proteins having a mol wt of 150-200 kDa and 14-20 kDa in cytosol. The affinity column of DE52 cellulose gave the main peak of cytosolic receptor at the KCl concentration of 1.5-2.5 M, demonstrating that the association of the 150-200 kDa with 14-20 kDa forms would depend on the ionic environment. The cytosolic 150-200 kDa protein, which had a high specificity to androgen, became lower in molecular weight to 14-20 kDa following DE52 cellulose column chromatography. The nuclear KCl extracted receptor, after dialyzing by Sephadex G-75 column, showed two peaks at 150-200 kDa and 14-20 kDa by Sephacryl S-200 column. The nuclear 150-200 kDa receptor was also associated with the 14-20 kDa protein by DE52-cellulose column at 1.5-2.5 M KCl. The binding eluate at 1.5-2.5 M KCl on DE52 was estimated to be a 14-20 kDa protein and was not dissociated into two forms by Sephacryl S-200. The androgen specificity to the nuclear 14-20 kDa binding protein was emphasized by high ionic strength. This report presented the evidence that the cytosolic high mol wt receptor had the same character as the nuclear receptor in ionic condition and that the cytosolic high mol wt receptor was composed of a nuclear receptor and nontransformed binding protein.

Androgen-Binding Protein↗
PubMed1985

The interaction of androgen and thyroid hormones in the submandibular gland of the genetically hypothyroid (hyt/hyt) mouse.

The development and maintenance of granular convoluted tubule cells in the mouse submandibular gland (SMG) and the production of renin-1, renin-2, and epidermal growth factor (EGF) by these cells are under complex hormonal control. Hypophysectomy causes profound involution and loss of renin activity in this gland. We have shown previously that T4 acts synergistically with 5 alpha-dihydrotestosterone (DHT) to restore SMG morphology and renin-2 activity in hypophysectomized female mice. Investigating the mechanism of T4 and DHT interaction in the hypophysectomized mouse proved impractical, and in the present study we have used genetically hypothyroid (hyt/hyt) mice that carry the structural gene for renin-1 but not for renin-2. Levels of SMG renin-1 and EGF in hyt/hyt mice were less than 4% of those in euthyroid (hyt/+) littermates. Administration of a pharmacological dose of T4 (2.5 micrograms/g BW X day, ip) to male hyt/hyt mice for 18 days restored SMG renin-1 and EGF to near-normal levels. The weights of SMG, seminal vesicle, and epididymis were also lower in hypothyroid mice and increased in response to T4. The effect on SMG renin-1 and EGF of either DHT (150 micrograms/g BW every other day, sc) or T4 (0.025-2.5 micrograms/g BW.day, ip) was blunted in female hyt/hyt mice. A combination of DHT and T4 (0.1 microgram/g BW.day) that restored total circulating T4 and T3 to physiological levels acted synergistically to increase SMG renin-1 and EGF. The administration of 2.5 micrograms T4/g BW.day plus DHT for 7 days increased the specific activity of SMG renin-1 and EGF to levels approaching those in euthyroid littermates given the same treatment. T4 (0.1 microgram/g BW.day) did not alter the quantity or sedimentation characteristics of high affinity androgen-binding protein in SMG from female hyt/hyt mice and induced SMG renin-1 in Tfm/Y mice. Thus, T4 does not appear to exert its effect via the androgen receptor. The administration of DHT and T4 to female hyt/hyt mice produced lower circulating levels of both T3 and T4 than the same dose of T4 given alone, suggesting that DHT does not act by enhancing the conversion of T4 to T3. This study demonstrates that the interaction of T4 and DHT is not a pharmacological phenomenon, but occurs at doses of T4 that restore serum T3 and T4 in female hyt/hyt mice to normal or near-normal levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗
PubMed2000

The ERK-1/2 signaling pathway is involved in the stimulation of branching morphogenesis of fetal mouse submandibular glands by EGF.

We have previously reported that epidermal growth factor (EGF) stimulates branching morphogenesis of the fetal mouse submandibular gland (SMG) (M. Kashimata and E. W. Gresik, 1997, Dev. Dyn. 208, 149-161) and that the EGF receptor (EGFR) is localized principally, if not exclusively, on the epithelial components of the fetal SMG (E. W. Gresik, M. Kashimata, Y. Kadoya, R. Mathews, N. Minami, and S. Yamashina, 1997, J. Histochem. Cytochem. 45, 1651-1657). The EGFR is a receptor tyrosine kinase, and after binding of its ligand, it triggers several intracellular signaling cascades, among them the one activating the mitogen-activated protein kinases (MAPK) ERK-1/2. Here we investigated whether EGF utilizes the ERK-1/2 signaling cascade to stimulate branching morphogenesis in the fetal mouse SMG. SMG rudiments were collected as matched pairs at E14, E16, and E18 (E0 = day of vaginal plug); placed into wells of defined medium (BGJb); and exposed to EGF for 5 or 30 min or to medium alone (controls). By Western blotting we found that EGF induced the appearance of multiple bands of phosphotyrosine-containing proteins, including bands at 170 kDa and 44 kDa/42 kDa, presumably corresponding to the phosphorylated forms of EGFR and ERK-1/2, respectively. Other blots showed the specific appearance of the phosphorylated EGFR and of phospho-ERK-1/2 in response to EGF. Immunohistochemical staining for phosphotyrosine increased at the plasma membrane after EGF stimulation for 5 or 30 min. Diffuse cytoplasmic staining for MEK-1/2 (the MAPK kinase that activates ERK-1/2) increased near the cell membrane after EGF stimulation. Phospho-ERK-1/2 was localized in the nuclei of a few epithelial cells after EGF for 5 min, but in the nuclei of many cells after EGF for 30 min. PD98059, an inhibitor of phosphorylation and activation of MEK-1/2, by itself inhibited branching morphogenesis and, furthermore, decreased the stimulatory effect of EGF on branching. Western blots confirmed that this inhibitor blocked phosphorylation of ERK-1/2 in fetal SMGs exposed to EGF. These results show that components of the ERK-1/2 signaling cascade are present in epithelial cells of the fetal SMG, that they are activated by EGF, and that inhibition of this cascade perturbs branching morphogenesis. However, EGF did not cause phosphorylation of two other MAPKs, SAPK/JNK or p38MAPK, in fetal SMGs. These results imply that the ERK-1/2 signaling is responsible, at least in part, for the stimulatory effect of EGF on branching morphogenesis of the fetal mouse SMG.

Animals↗
PubMed1995

Muscarinic receptor subtypes in the submandibular gland and the urinary bladder of the rabbit: in vivo and in vitro functional comparisons of receptor antagonists.

1. In pentobarbitone-anaesthetized rabbits, the inhibitory effects of muscarinic receptor antagonists with different selectivity profiles were examined on carbachol-evoked submandibular secretion and urinary bladder contractions, and on parasympathetically nerve-evoked secretion. On isolated submandibular gland fragments, the inhibitory effects of the antagonists were studied on carbachol-evoked release of potassium and on the overflow of tritium in response to electrical field stimulation. 2. In vivo, 4-DAMP equipotently inhibited simultaneously carbachol-evoked submandibular secretory and contractile responses of the urinary bladder, while pirenzepine was found to be four times as potent in inhibiting the secretory response compared with the contractile response. 3. The inhibition of carbachol-evoked salivation caused by atropine, 4-DAMP and pirenzepine was as great as their inhibition of parasympathetic nerve-evoked salivation. Methoctramine exerted less inhibitory effect on nerve-evoked salivation than on carbachol-evoked, thus seemingly causing greater presynaptic inhibition. 4. In vitro, pirenzepine was only 30 times less potent in inhibiting carbachol-evoked potassium release than 4-DAMP (pA2, 9.58 vs 8.10). Whereas atropine, 4-DAMP and pirenzepine abolished the overflow of tritium from isolated glands in response to electrical field stimulation, methoctramine increased it. 5. It is concluded that the muscarinic secretory response in the rabbit submandibular gland is exerted via both muscarinic M1 and M3 receptors, while the contractile response of the urinary bladder to muscarinic agonists is exerted via muscarinic M3 receptors. The release of acetylcholine from nerve terminals in the gland can be inhibited via M2 autoreceptors in rabbits.

Animals↗