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PubMed1989

Increase of muscarinic cholinergic receptors in the rat submandibular glands after parasympathectomy and repeated administration of haloperidol.

1. The mechanisms of the supersensitivity to cholinergic drugs after chronic haloperidol was studied in normal and parasympathectomized submandibular glands of the rats. 2. Both parasympathectomy and haloperidol treatment for 7 days (2 mg/kg/day, i.p.) increased the sialogogue response of the glands to methacholine, a cholinomimetic drug. 3. Both denervation and haloperidol administration induce up-regulation of the muscarinic receptors as expressed per gram of the tissue. 4. Haloperidol causes no further increase in sensitivity than denervation alone. 5. These data demonstrate that secretory supersensitivity to cholinergic drugs in the rat submandibular glands, after chronic haloperidol and parasympathectomy is related to an increase in muscarinic cholinergic receptors.

Animals↗
PubMed1991

A potent vasoconstrictor in the rat submandibular gland.

We detected a novel vasoconstrictor in an arginine esterase fraction separated from fractions containing tonin and other esterases that were obtained from a rat submandibular gland extract. When tested on isolated rabbit aorta rings, the substance caused dose-related contractions that were slow in onset, long-lasting, and difficult to reverse by rinsing. The substance acts directly on vascular smooth muscle, since preincubation with plasma or intact endothelium is not required. The fact that the constrictor was destroyed by heat and incubation with pronase suggests that it is a protein. Molecular sieving indicates an estimated molecular weight of 24,000 Da. It has a neutral isoelectric point that is higher than the pI of tonin, from which it can be separated by anion exchange chromatography. A small amount of the vasoconstrictor was obtained by gel filtration and eluted from isoelectric focusing polyacrylamide gels. The purified substance showed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was a potent vasoconstrictor; an estimated concentration of 2.5 nM induced contraction of isolated rabbit aorta rings ranging from 15% to 40% of the maximum contraction obtained by 60 mM KCl. Contraction was completely blocked by 1 mM (p-amidinophenyl)methanesulfonyl fluoride, a serine protease inhibitor. Contractile activity was not affected by hirudin, a thrombin inhibitor, but was completely inhibited by soybean trypsin inhibitor and blunted by aprotinin; thus it may be a trypsin-like serine protease. Purified vasoconstrictor preparation showed hydrolyzing activity on Pro-Phe-Arg-methyl-coumarin amide, a kallikrein substrate. We conclude that a novel vasoconstrictor serine protease is present in the rat submandibular gland.

Animals↗
PubMed1983

[Experimental studies on regeneration of myoepithelial cells--the rat submandibular gland autografted in the tongue].

The regeneration process of myoepithelial cells in the injured salivary gland was studied. Fragments of the rat submandibular gland autografted in the tongue were examined from 12 hours to 14 days after implantation by means of the methods of autoradiography, histochemistry and electron microscopy. Two days after implantation, the central area of the fragments showed necrosis and parenchymal regeneration was, on the other hand, revealed at the remaining periphery. It was demonstrated by [3H] thymidine autoradiography that the regeneration of the intralobular parenchyma took place at the remaining intercalated and striated portions of the duct, but never did at the secretory endpieces. Initially, solid cell clusters were composed of regenerating uniformly immature polygonal epithelial cells. Four days after implantation, intracytoplasmic filaments running parallel to the plasma membrane of the cell, measured 50-70 A in diamter, were detected in some cells of the cluster. These filaments were accompanied by dense bodies characteristic of those of smooth muscle cells, and were thereby identified with myofilaments. Based on the findings, the regenerating cells with myofilaments were recognized as immature myoepithelial cells. Showing mosaic arrangement, they intermingled with the other kind of regenerating epithelial cells in the cluster. Each regenerating cell cluster formed gradually tubular structure with epithelial stratification. Ten days after implantation, most tubular structures were consisted of the single layer of columnar or cuboidal cells. Fourteen days after implantation, alkaline phosphatase activity characteristic of mature myoepithelial cells was observed in the spindle cells located between tubular epithelium and basal lamina. Ultrastructurally these spindle cells were identified with mature myoepithelial cells because of furnishing myofilaments with dense bodies. The results of this experiment suggest that, in case of tissue injury, the epithelial regeneration in the intralobular portion of the salivary gland is initiated at the intercalated and/or striated portions of the duct, and followed by myoepithelial differentiation of some of the regenerating epithelial cells.

Animals↗
PubMed1993

Differential effect of submandibular gland resection on the growth of pancreatic cancer in cheek pouch and subcutaneous tissue.

Exogenous administration of epidermal growth factor (EGF) enhances tumor growth of H2T, a hamster pancreatic cancer that is inoculated in the cheek pouch. The effect of endogenous EGF on tumor growth, however, is not known. The main source of EGF in the body is the submandibular glands. This study examined the influence of submandibular gland resection (SMx) on H2T tumor growth in the cheek pouch and compared it to the growth in SC tissue. Bilateral SMx or sham operation was performed on male Syrian golden hamsters. In 30 hamsters (n = 15 for each operation group), 5 x 10(4) and 5 x 10(5) H2T cells were inoculated in the bilateral cheek pouches and intrascapular SC tissue, respectively (Exp. 1). In another 30 hamsters (n = 15 for each operation group), 5 x 10(5) and 1 x 10(6) H2T cells were inoculated at the same sites (Exp. 2). Two longest perpendicular diameters of the tumor were measured once a week for 12 wk (Exp. 1) or 8 wk (Exp. 2), and the tumor area was calculated. The tumor area in the cheek pouch became significantly smaller in the SMx group than the sham-operated group after the 8th wk (Exp. 1) or the 7th wk (Exp. 2). On the other hand, the tumor area in the SC tissue did not show any difference between groups through the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Distribution of nerve growth factor in the submandibular gland of the male and female mouse. A re-examination by use of an improved immunohistochemical procedure.

Nerve growth factor (NGF) was localized in the mouse submandibular gland by means of indirect immunofluorescence applied to 0.5 micron-thick sections of freeze-dried, plastic-embedded tissue. The antibody to NGF (IgG-fraction) was raised in rabbits immunized with pure 2.5 S NGF from submandibular glands of adult male mice. In the male gland anti-NGF bound selectively to the secretory granules was present in the cells of the granular ducts. Immunoreactive granules extended from the perinuclear region toward the apical pole. In the female gland immunoreactive cells and granules were considerably less abundant than in males. Immunofluorescence was confined to individual secretory cells located in the wall of the granular striated duct. In the present study no support was found for the hypothesis suggesting that immunoreactive NGF is formed within the secretory granules during their transport from the perinuclear region to the apical pole.

Animals↗
PubMed1986

Induction of a specific (LM) protein in the submandibular gland of the rat by repeated amputation of the lower incisor teeth.

Chronic administration of the beta-adrenergic agonist isoproterenol (IPR) leads to marked hyperplastic/hypertrophic enlargements of the parotid and submandibular glands in rats and mice with concomitant changes in the composition of both the glands and the saliva. Conspicuous among the alterations of the submandibular saliva is the appearance of a 13,000 Mr protein, termed LM (large mobile) protein. Repeated amputation of the lower incisor teeth also causes enlargements of the major salivary glands in rats. In this study, we have compared the enlargements of submandibular glands of rats produced by IPR administration or teeth amputation with respect to the relative levels of the LM protein in gland extracts and saliva. Administration of IPR-HCl (40 mg/kg) twice daily for 5 days or amputation of the lower incisor teeth 3 times a week for 3 weeks resulted in a 2.2-fold increase in the weight of the submandibular gland. Amputation for one week led to a 1.4-fold increase in gland weight. Double immunodiffusion in agar antibodies against the purified LM protein gave a single precipitin line with gland extracts and saliva of IPR-treated and teeth-amputated rats, indicating immunological identity of the reacting antigens. No precipitin lines were seen with gland extracts or saliva of untreated rats. Immunoblots of pooled saliva obtained from IPR-treated or teeth-amputated rats revealed a single protein band of the same electrophoretic mobility in SDS-polyacrylamide gels when stained using anti-LM antibodies. The relative concentrations of LM protein in gland extracts and saliva were measured by a solid-phase enzyme-linked immunoabsorption assay using antibodies against the purified LM protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of carbamylcholine and isoproterenol on electrolyte fluxes in perfused main duct of submandibular gland of reserpinized rat.

Administration of reserpine (RES) at a dosage of 0.5 mg/kg body wt, ip daily for 7 days was found to lower the dose of carbamylcholine and isoproterenol that alters sodium and potassium transport by cells of the main duct of rat submandibular gland. In the perfused main excretory duct of the submandibular gland of the RES rat, administration of carbamylcholine at a dosage of 1 microgram/kg body wt, inhibited net efflux of sodium (17%) and administration of isoproterenol at a dosage of 2 micrograms/kg body wt increased net efflux of sodium (20%); these drugs, at the same dosages, did not induce significant change in electrolyte flux of normal rat. At a dosage of 5 micrograms/kg body wt, carbamylcholine decreased net influx of potassium (15%) in the RES rat but was without effect on normal rat. Isoproterenol at the dosage of 5 micrograms/kg body wt significantly inhibited net influx of potassium in both the RES rat and normal rat. The data suggested that the duct cells developed supersensitivity to sympathomimetic and parasympathomimetic stimulation after chronic RES treatment.

Animals↗
PubMed1996

CT of submandibular gland sialolithiasis.

We emphasise the importance of high-resolution CT with reconstruction in the demonstration of submandibular gland (SMG) sialolithiasis and its role in monitoring treatment. We studied 76 patients with swollen and tender SMG, some with fever. They underwent conventional radiography, sonography (US) and high-resolution CT with reconstructions. Conventional radiographs demonstrated single stones in 29 patients. Axial CT, before reconstructions, demonstrated single stones in 63 patients and multiple stones in another 5. Following CT reconstructions, multiple stones were demonstrated in 37 patients. On US stones were diagnosed in only 33 patients, and multiple stones in only 1. All 68 patients with stones shown on imaging and 2 without stones underwent surgery, with good clinical results. Total removal of the SMG and its duct was performed in patients with multiple stones, chronic inflammatory changes in the SMG, or a solitary stone in the SMG or deep in the duct. A small incision for removal of a solitary stone in the distal aspect of Wharton's duct was performed in 15 patients, with excellent clinical results. Another 14 patients with multiple salivary gland stones, diagnosed on CT reconstructions, did not improve following this procedure and needed further surgery; clinical improvement occurred following excision of the SMG and Wharton's duct. Histological examination in all of these confirmed the presence of additional stones. Conservative anti-inflammatory treatment was recommended for 6 patients in whom CT reconstructions did not demonstrate stones.

Adult↗
PubMed2001

Hydroxychloroquine enhances the endocrine secretion of adenovirus-directed growth hormone from rat submandibular glands in vivo.

Use of gene transfer technology for treating single protein deficiency disorders requires delivery of therapeutic levels of the transgene product. We have suggested that salivary glands may provide a potentially valuable target site for certain systemic applications of gene therapeutics (He et al., Gene Ther. 1998;5:537-541). However, the ability of salivary glands to deliver therapeutic proteins to either the upper gastrointestinal tract via saliva or to the bloodstream, as required, must be carefully evaluated. In the anterior pituitary gland, human growth hormone (hGH) is secreted into the bloodstream via the regulated secretory pathway. However, when expressed from an adenoviral vector delivered to salivary glands, most hGH follows the regulated, tissue-specific, exocrine secretory pathway into saliva, where it is not therapeutically useful. We tested the hypothesis that the commonly used, FDA-approved drug hydroxychloroquine (HCQ) can divert adenovirus-directed hGH from this regulated secretory pathway in rat submandibular glands and enhance delivery into the bloodstream. In untreated rats, there was approximately 20-fold more vector-directed hGH in saliva than in serum. Administration of HCQ led to a shift of hGH secretion into the bloodstream. When delivered at doses of 1 or 10 mg/kg body weight, via intraperitoneal injection plus intraductal infusion, the saliva:serum hGH ratio was approximately 2:1. Such HCQ delivery did not significantly alter the total amount of hGH measured, but increased the serum level of hGH 5- to 6-fold. Also, HCQ had no significant effects on serum chemistries or hematological parameters. We conclude that HCQ is able to significantly enhance hGH secretion from salivary glands into the bloodstream and may be useful to facilitate clinical applications of gene therapeutics via salivary glands.

Adenoviridae↗
PubMed1979

Dynamics of beta adrenoceptor induced amylase release and cyclic AMP accumulation in the guinea pig submandibular gland.

The dynamics of amylase release from the guinea pig submandibular gland were studied in vitro by applying a multi-channel microperfusion set. This technique makes it possible to measure time related enzyme release more accurately and to take samples of perifused tissue at short intervals. Stimulation of the beta-adrenoceptor with norepinephrine gives rise to a rapid initial enzyme discharge, detectable within 15 s. Administration of propranolol inhibits enzyme release, which is not restored after removal of the agent. Simultaneous measurements of tissue cyclic AMP during norepinephrine stimulation at various time intervals display a significant increase of cAMP as early as 15 s after stimulation of secretion. This increase of cAMP thus coincides with the discharge of amylase. In addition, cAMP continuously accumulates during 30 min of norepinephrine perifusion of the slices. The present study describes a valuable tool with high sensitivity for visualizing the relations between enzyme secretion from the salivary gland and the intracellular biochemical processes. The data obtained further indicate a close correlation between amylase and cAMP during the initial phase of enzyme discharge.

Amylases↗
PubMed1989

Effects of tachykinins on the secretion of fluid and glycoproteins from the submandibular glands of rat, mouse, hamster and guinea pig.

The effects of substance P, neurokinin A, physalamine, and eledoisin on the secretion of fluid and glycoproteins from the submandibular glands of various rodents were investigated. Following i.v. injection of each peptide at a dose of 20 micrograms/kg, the major glycoprotein species secreted from rats and guinea pigs were shown to be electrophoretically identical with those found in the acini. However, saliva was not elicited from the mice and hamsters. These results suggest that in both rats and guinea pigs, tachykinins act on the acinar cells of the submandibular gland only.

Animals↗
PubMed1998

Distribution of H type 1 and of H type 2 antigens of ABO blood group in different cells of human submandibular gland.

We have examined the immunohistochemical distribution of H Type 1 and of H Type 2 substances of the ABO blood group system in human submandibular gland using either of the two anti-H monoclonal antibodies MAb 1E3 and MAb 3A5. MAb 3A5 was specific for H Type 2, and MAb 1E3 reacted with each of H Type 1-H Type 4 artificial antigens. We have developed a competitive inhibition method against H Type 2 and have obtained MAb 1E3, which is fairly specific for H Type 1 under certain conditions. Mucous cells from secretors were strongly stained by 1E3 and weakly by 3A5, whereas those from nonsecretors showed no reaction with 1E3 and 3A5. Serous cells from both secretors and nonsecretors were stained neither by 1E3 nor by 3A5. Striated and interlobular duct cells were strongly stained by 1E3 and by 3A5, regardless of the secretor status. These results indicated that the expressions of the H Type 1 and H Type 2 in different cell types of the submandibular gland were controlled by different genes. In addition, we have determined the acceptor specificity of two alpha(1,2)fucosyltransferases (H and Se enzymes) after transient expressions of the FUT1 and FUT2 in COS7 cells, and found that the H enzyme activity was similar for both Type 1 and Type 2 precursors, and that Se enzyme activity with the Type 1 precursor was higher than that with the Type 2 precursor. Expression of the H Type 1 antigen in mucous cells was found to be dependent on the Se gene, whereas expressions of the H Type 1 and H Type 2 antigens in striated and interlobular duct cells were dependent on the H gene. (J Histochem Cytochem 46:69-76, 1998)

ABO Blood-Group System↗
PubMed1987

Bilateral submandibular gland lymphoma in Sjögren's syndrome.

Salivary gland lymphoma is associated with Sjögren's syndrome. A case of bilateral submandibular gland and sublingual gland lymphoma, arising in Sjögren's syndrome, is presented. A lymphoma involving more than one salivary gland may occur in Sjögren's syndrome, and there is an increased risk of developing an extrasalivary lymphoma.

Female↗
PubMed1986

Ultrastructure of the submandibular gland in 2 species of macaques.

The ultrastructure of the submandibular glands was studied in 2 species of macaques (Macaca mulatta and Macaca irus). The glands, which were identical in both species, were predominantly serous, but contained scattered mucous acini. The serous cells contained 1 of 2 morphologically distinct secretory granules of complex substructure, whereas mucous droplets were relatively simple in structure. Other parts of the macaque glands were similar to their counterparts in other primates. The close resemblance of the serous granules to each other in the 2 species studied and to 3 other macaque species previously described by others suggests that these monkeys are taxonomically closely related.

Animals↗
PubMed1989

Epithelial shape change in mouse embryonic submandibular gland: modulation by extracellular matrix components.

Early morphogenesis of mouse submandibular gland provides an excellent model for the formation of epithelial lobules as a consequence of epithelial-mesenchymal interactions. Both proteoglycans and a glycosaminoglycan, high molecular weight components which contain amino-sugars and hexuronic acids, seem to be important in maintaining the lobular structure through the formation of epithelial basal lamina. Collagen also appears to play a crucial role in this morphogenesis. By visualizing the distribution of collagen fibrils and by changing the concentration of collagen in the gland, we have developed a new hypothesis which emphasizes the mechanical role of mesenchyme in epithelial cleft formation. Precise mechanisms for the involvement of these molecules have not been elucidated, yet it is now clear that knowledge of the function of the extracellular matrix components is a prerequisite for understanding the epithelial-mesenchymal interactions.

Animals↗
PubMed1985

31P-NMR study of dog submandibular gland in vivo and in vitro using the topical magnetic resonance.

The topical magnetic resonance (TMR) was used to study the phosphorous metabolism of a dog's submandibular gland during acetylcholine stimulation. The experiments were carried out under two conditions. One was a normal blood supply (in vivo) and the other was vascular perfusion with the artificial perfusate (in vitro). The levels of phosphorous compounds in the gland were obtained for 31P-NMR spectra of the TMR. The saliva was secreted in the both conditions, though the salivary flow under the in vivo condition was higher than in vitro. During salivary secretion, only the levels of creatine phosphate decreased under in vivo condition, while the levels of creatine phosphate and ATP decreased and the levels of inorganic phosphate increased in in vitro cases. It was concluded that the decrement of creatine phosphate during the salivary secretion indicates the acceleration of the energy metabolism in the submandibular gland.

Acetylcholine↗
PubMed2006

Cytomorphological study on human submandibular gland following treatment with secretagogue drugs.

Using specimens of human submandibular glands, we have investigated in vitro the morphological modifications induced by clozapine, a dibenzodiazepine derivative that is used in psychotic patients and that provokes hypersalivation, a side-effect of therapy. The effects of the drug, used alone or in combination with carbachol, have been compared with those observed after treatment with drugs acting on specific receptors. To quantify the response to stimulation, we have calculated (with statistical methods) the number of microvilli and microbuds (corresponding to pits seen in images obtained by transmission electron microscopy) per square micrometre of the cytoplasmic surface of the intercellular canaliculi luminal membrane in images obtained by high-resolution scanning electron microscopy. Clozapine, when directly acting on human submandibular specimens, induces a small secretory response in serous cells; this is partially decreased by muscarinic and adrenergic antagonists and by combined incubation with carbachol, thus confirming its behaviour as a partial agonist to muscarinic receptors. We also suggests that the drug acts on the nerve terminals contained within the glandular specimens.

Adult↗
PubMed2005

[Granular cell tumor -- a rare tumor lesion of submandibular gland origin].

RATIONALE: Granular cell tumors are rare entities with manifestations in nearly all organ systems. Appearance in salivary glands is observed in singular cases. CASE REPORT: We report a 54 years old female patient with a painless submandibular tumor lesion. Using a submandibular approach the tumor was totally removed with the submandibular gland. Histologically a benign granular cell tumor was diagnosed. The immunohistological examination revealed positive for S-100 antigen and vimentin, negative for KL1 antigen. The clinical follow-up for about 3 years was without complications or tumor recidive. CONCLUSIONS: A differential diagnosis of a submandibular mass is the rare manifestation of a benign granular cell tumor. The neurogen origin can be proven immunohistologically by positive S-100 antigen detection. The complete surgical resection is the therapy of choice.

Biomarkers, Tumor↗