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PubMed1998

Chloride transport in a human submandibular gland cell line studied by X-ray microanalysis.

Ion transport properties of the human submandibular gland cell line A253 were investigated by X-ray microanalysis. The cells were grown on ultrathin plastic films on titanium grids. After the experiment, where the cells were exposed to various agonists and inhibitors, the specimens were briefly rinsed in distilled water, frozen, and freeze-dried. The elemental composition of the cultured cells most closely resembled that of striated duct cells. Beta-adrenergic stimulation caused a small decrease in the cellular Cl- and K+ concentration, but cholinergic stimulation had no effect. Also stimulation with cAMP caused a decrease in Cl- and K+; this decrease could be inhibited by the chloride channel blocker NPPB. Loss of Cl- and K+ could also be elicited by exposure to a hypotonic solution. The results suggest that there may be several types of chloride channel present in A253 cells.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1996

Transepithelial fluid shift generated by osmolarity gradients in unstimulated perfused rat submandibular glands.

The effects of osmotic gradients on transepithelial water movements were examined in unstimulated perfused submandibular glands of the rat. Osmotic gradients were applied transepithelially by adding sucrose to or removing it from the perfusate. An infusion of hypotonic perfusate shifted fluid from the interstitium to the lumen (luminal fluid shift) transiently, whereas an infusion of hypertonic perfusate shifted fluid from the lumen to the interstitium (interstitial fluid shift) transiently. The amount of fluid shifted from lumen to interstitium increased as the luminal fluid osmolarity was raised or as the perfusate osmolarity was reduced. Thus, fluid movements across the salivary epithelium were shown to be simply dependent on the osmolarity difference between lumen and interstitium. To estimate the effective pore radius of the epithelium, non-electrolyte solutions (urea, dimethylurea, diethylurea, mannitol, sucrose and maltotriose) were also used as luminal solutions. The results from non-electrolyte experiments showed that the effective pore radius of the passage for non-electrolytes was slightly larger than 0.38 nm. Solutes smaller than mannitol were less effective in opposing the interstitial fluid shift, and the value of effective pore radius in this report was similar to that of the secretory water pathway that has been measured in solvent drag studies (0.4 0.45 nm). These findings suggest that the passage for non-electrolytes may be water transport pathway in salivary epithelium.

Animals↗

PubMed1978

Morphology and cytochemistry of acinar secretory granules in normal and isoproterenol-treated rat submandibular glands.

Several fixation procedures have been utilized in a fine-structural study of rat submandibular glands with the aim of correlating the morphology of granule substructure with its composition. Procedures included fixation with aldehyde in a variety of buffers, with or without fixation additives such as tannic acid or calcium chloride. Both immersion and perfusion fixation studies were performed. Osmium tetroxide postfixed tissue was compared with non-postfixed tissue. Thin sections were stained for carbohydrate-containing constituents by either periodic acid-thiocarbohydrazide-silver proteinate or tannic acid-ferric chloride sequences. The morphology and cytochemistry of acinar secretory granules were highly dependent upon the fixation procedure utilized. In postfixed tissue, fine filaments and vesicles were the major granule constituents. Filaments often aggregated into fibrils in fixatives containing phosphate buffer or calcium, whereas vesicles were prominent with fixatives containing collidine buffer. Tannic acid, as a fixation additive, imparted enhanced density to the peripheral rim of aggregated filaments. If post fixation was eliminated, an amorphous meshlike material was the major granule component. This stained readily with methods for carbohydrate whereas the granules of post-osmicated tissue did not. Following chronic isoproterenol treatment the degree of filament aggregation in postfixed tissue was augmented, and this corresponded to an increase in amount of material stainable for carbohydrate in non-post-osmicated tissue.

Animals↗

PubMed1997

Characterization and localization of P2 receptors in rat submandibular gland acinar and duct cells.

[Ca2+]i and the Cl- current were measured in isolated submandibular gland acinar and duct cells to characterize and localize the purinergic receptors expressed in these cells. In both cell types 2'-3'-benzoylbenzoyl (Bz)-ATP and ATP increased [Ca2+]i mainly by activation of Ca2+ influx. UTP had only minimal effect on [Ca2+]i at concentrations between 0.1 and 1 mM. However, a whole cell current recording showed that all nucleotides effectively activated Cl- currents. Inhibition of signal transduction through G proteins by guanyl-5'-beta-thiophosphate revealed that the effect of ATP on Cl- current was mediated in part by activation of a G protein-coupled and in part by a G protein-independent receptor. BzATP activated exclusively the G protein-independent portion, whereas UTP activated only the G protein-dependent portion of the Cl- current. Measurement of [Ca2+]i in the microperfused duct showed that ATP stimulated a [Ca2+]i increase when applied to the luminal or the basolateral sides. BzATP increased [Ca2+]i only when applied to the luminal side, whereas UTP at 100 microM increased -Ca2+-i only when applied to the basolateral side. The combined results suggest that duct and possibly acinar cells express P2z receptors in the luminal and P2u receptors in the basolateral membrane.

Adenosine Triphosphate↗

PubMed2002

Probing for submandibular gland peptide-T receptors on leukocytes with biotinylated-Lys-[Gly](6)-SGP-T.

Submandibular gland peptide-T (SGP-T) is a potent anti-chemotactic agent for human neutrophils possessing anti-inflammatory properties. Biologically active analogues of SGP-T have been synthesized and a biotinylated form (KG(6)-SGP-T; Bio-KG(6)-SGP-T) was utilized to identify binding sites on isolated human neutrophils. Neutrophils incubated with Bio-KG(6)-SGP-T followed by phycoerythrin (PE)-avidin secondary reagent were fixed and visualized using histochemistry and flow cytometry. At doses of 10(-8) and 10(-9) M, Bio-KG(6)-SGP-T was shown to bind to neutrophils. The binding of Bio-KG(6)-SGP-T, at doses of 10(-8) and 10(-9) M, to neutrophils was abolished by a 100-fold excess of non-biotinylated peptide (KG(6)-SGP-T), but not by 100-fold excess of SGP-T. However, all peptides, dose-dependently reduced the binding of a CD16b antibody (LNK16 clone) to isolated human neutrophils. This discrepancy probably results from different preferred conformations for Bio-KG(6)-SGP-T, KG(6)-SGP-T and SGP-T, since exhaustive conformational searches revealed a high degree of overlap between alpha-Bio-KG(6)-SGP-T and KG(6)-SGP-T that was not seen with SGP-T.

Antibodies↗

PubMed1999

Thyroid hormone (3,5,3'-triido-L-thyronine) masking/inversion of stimulatory effect of androgen on expression of mk1, a true tissue kallikrein, in the mouse submandibular gland.

We studied hormonal regulation of the expression of mkl, a true tissue kallikrein, in the submandibular gland (SMG) of ICR, C3H/ HeN, and F1 (mice from male C3H/HeN x female ICR and in the ones from male ICR x female C3H/HeN). In these mouse strains, mk1 was low in content in males, abundant in females, and increased remarkably by castration of males. In the case of ICR and both F1 mice, injection of 5alpha-dihydrotestosterone (DHT) reduced the mkl level of castrated and female mice. However, the mkl content in female C3H/ HeN mice (or castrated C3H/HeN) was further increased by DHT. To investigate the real action of DHT on mk1 expression, we examined the effects of adrenoectomy/glucocorticoid (dexamethasone, Dex) administration; DHT administration into castrated and adrenoectomized mice; ovariectomy/female hormone (17beta-estradiol, progesterone) administration; and hypophysectomy/combinatory administration of DHT, Dex, and thyroid hormone (3,5,3'-triiodo-L-thyronine, T3) on the mk1 expression in the SMG of ICR mice. Adrenoectomy or ovariectomy did not change the characteristic pattern of mk1 expression in male and female ICR mice. In hypophysectomized (Hypox) ICR male mice, the mk1 content was increased to the same level as in normal ICR females, and DHT administration into the Hypox mice further increased the mk1 level. However, combinatory administration of DHT + T3 or of DHT + T3 + Dex into the Hypox mice lowered the mkl content to the level of normal ICR males, whereas T3 single administration had no effect. Dex single administration into the Hypox mice increased the mkl level to an even higher than that observed with DHT administration. The mk1 level in Hypox mice was not significantly changed by coadministration of Dex with T3. From these results, we conclude that 1) mk1 expression is fundamentally stimulated by androgen (DHT) as are other mk isozymes, such as mk9, mk13, mk22, and mk26 in the mouse SMG, 2) the effect (stimulatory) of DHT on mk1 expression becomes, however, inverted (inhibitory) in the presence of T3. Although the serum T3 level of C3H/HeN female (0.52 ng/ml) was not significantly different from that of C3H/HeN males or ICR mice, coadministration of T3 into C3H/HeN females with a fixed amount of DHT (20 mg/kg body weight) dose dependently repressed the DHT-induced increase in mkl expression, suggesting the lower sensitivity of C3H/HeN females to T3.

Adrenal Glands↗

PubMed1993

Case report: congenital fistula between the submandibular gland and the oropharynx.

Congenital salivary fistulae are rare and may be associated with abnormalities of the branchial apparatus or arise from aberrant or accessory salivary tissue. Previous case reports have documented cutaneous fistulae. We report a case of a salivary fistula between the submandibular gland and the oropharynx and discuss a possible embryological basis for the abnormality.

Adult↗

PubMed1991

The effect of ageing on mucin contents in mouse submandibular glands.

There may be deleterious effects if there is an age-dependent reduction in mucin composition or content in salivary glands. To assess whether there was an effect of age in submandibular glands from male mice aged 3 months, 10 and 20 months and 27, 29 and 30 months, mucin, protein and sialic acid were quantitated. Changes in wet weight per gland and protein per gland were highly significant (p less than 0.001), as tested by analysis of variance, and the means for both were highest in middle aged glands. While sialic acid per gland showed no significant change from middle aged to old glands, mucin per gland showed an age-related decrease (p less than 0.01) when comparing either young or middle aged glands with old glands.

Aging↗

PubMed1994

The localization of basic fibroblast growth factor (FGF-2) in rat submandibular glands.

The immunohistochemical localization of basic fibroblast growth factor (FGF-2) in the submandibular glands of the rat was investigated by use of an antiserum to FGF-2. Nerve fiber bundles with FGF-2-immunoreactivity were found in association with interlobular ducts and blood vessels; they dissociated into single immunoreactive nerve fibers perhaps to terminate in proximity to acinar cells, or to form a reticular fiber network within the tunica adventitia of blood vessels. The FGF-2-immunoreactive neurons were located in the submandibular ganglia, but not in the superior cervical ganglia; hence, at least some of these immunoreactive nerve fibers probably come from the submandibular ganglia and are of parasympathetic origin. Most of the epithelial cells of the intercalated and collecting ducts showed notable FGF-2 immunoreactivity. The characteristic distribution of FGF-2 immunoreactivity in both the neuronal and epithelial tissues of the salivary glands suggests a role of this growth factor in complex physiological processes within the salivary glands.

Animals↗

PubMed1984

CT scanning of tumors in or near the parotid or submandibular glands. A comparison with conventional sialography.

Plain computed tomography (CT) scanning and CT scanning after injection of contrast medium into the salivary glands (CT sialography) were compared with conventional sialography in 50 patients with neoplasms in or near the parotid or submandibular glands. The results were correlated with clinical and pathological findings. CT sialography proved to be the best diagnostic method in the diagnosis of salivary gland tumors.

Adenolymphoma↗

PubMed1992

Characterization of superior cervical ganglion neurons that project to the submandibular glands, the eyes, and the pineal gland in rats.

These studies sought to determine whether the cell bodies of rat superior cervical ganglion neurons projecting to three very different target organs differ in terms of their size, number, location within the ganglion and/or neuropeptide content, and whether these features are altered in response to neonatal deafferentiation of the ganglion. A series of retrograde tracer, immunocytochemical, and double-labeling studies revealed differences in the size, number, location and neuropeptide content of superior cervical ganglion neurons that project to the submandibular salivary glands, eyes, or pineal gland. The mean areas of the cell bodies of neurons projecting to the submandibular gland are largest, those projecting to the eye are smallest, and those projecting to the pineal are intermediate in size. Submandibular gland projecting neurons are found throughout the ganglion, while the eye and pineal projecting populations are localized to the rostral quadrants. The different subpopulations of target organ specific superior cervical ganglion neurons are heterogeneous in their content of vasoactive intestinal peptide-, neuropeptide Y- and somatostatin-like immunoreactivity. A greater percentage of submandibular gland than of pineal projecting neurons display vasoactive intestinal peptide-like immunoreactivity, but there are no differences in the percentage of neurons displaying neuropeptide Y- or somatostatin-like immunoreactivity between the target organ specific groups. Neonatal deafferentiation does not result in changes in the size, number or distribution of target organ specific neurons, or in the percentage of immunoreactive neurons in these populations. In conclusion, these studies provide evidence that the size and distribution of neurons and percentage of peptide-containing neurons in the superior cervical ganglion is related to the target organ innervated, but provides no evidence of exclusive target organ-peptide relationships.

Afferent Pathways↗

PubMed2005

Submandibular gland sialolith in a renal transplant recipient: a case report.

Salivary dysfunction may be due to systemic diseases and medications. The development of sialoliths is a multifactorial event in which disturbances in secretion, microliths, and bacteria may play a major role. A case of sialolith in the submandibular gland of a 58-year old woman, with a medical history of renal failure end kidney transplant, is reported.

Female↗

PubMed1991

Experimental autoallergic sialadenitis in the LEW rat. II. Target antigens are associated with cell surface and intracellular particulate fractions derived from the submandibular gland.

Experimental autoallergic sialadenitis (EAS) in the LEW rat is an autoimmune lymphocytic destruction of the submandibular gland (SMG) induced by sensitization with an SMG homogenate emulsified in adjuvant. Here we report that the antigens in the SMG homogenate involved in the induction of EAS can be localized to both cell-surface and intracellular particulate fractions. Differential centrifugation procedures were used to isolate 10,000g, 25,000g, 40,000g, and 100,000g particulate fractions from the SMG of LEW or WF rats. The particulate SMG fractions were used to sensitize female LEW rats for EAS induction. Since the protein concentrations of the fractions varied as a percentage of their composition in the whole homogenate, additional experiments were performed using equivalent protein concentrations for sensitization. Two weeks after sensitization, the SMGs of the sensitized animals were recovered and processed for histologic examination. Samples of the SMG fractions used for sensitization were also examined by electron microscopy. The 25,000g and 100,000g fractions consistently induced extensive mononuclear cell infiltrates and exocrine gland destruction in the SMGs while the 10,000g and 40,000g fractions caused infrequent and minimal inflammatory cell infiltrates in the glands. These data, combined with the electron microscopic analysis of the fractions, suggest that the target antigens in EAS reside on particulate fractions from the SMG that have the characteristics of the cell surface (25,000g) and microsomes (100,000g).

Animals↗

PubMed1992

An immunohistochemical study of the distribution of ABH antigens in human submandibular glands at the light and electron microscopic levels.

The distribution of blood group antigens ABH in submandibular glands was studied at light and electron microscopy levels by applying ImmunoGold Silver Staining (IGSS) and post-embedding ImmunoGold (IGS) methods, respectively. In IGSS treated samples, a cytoplasmic and a surface form of antigen localization were discernible in the glandular parenchyma. The former was restricted to most mucous cells and to scattered serous cells: A and B antigens were demonstrated in mucous cells of A and B type glands, while H antigen appeared in most mucous and occasional serous elements regardless of the blood type of donors. The latter appeared as a strong H reactivity on cell surfaces of serous acini and ducts regardless of the patient blood type. The IGS method was applied both on non-osmicated samples embedded in LR White resin and on osmicated, Epon embedded samples. In non-osmicated tissues, antigen labelling was revealed in secretory granules and cell surfaces. Positive secretory granules were found in most mucous cells and occasional serous, intercalated, and striated duct cells. A and B antigens weakly reacted in mucous cells of A and B type glands, respectively, while strong H reactivity was seen in mucous, serous, intercalated and striated duct cells of glands of all types. Surfaces labelled with H antigen were found on both lumenal and basolateral membranes of striated ducts in glands of all types. IGS method applied on osmicated, Epon embedded samples, selectively revealed blood group antigens in secretory granules of serous cells but not in the apical vesicles of striated ductal cells. Cell surfaces were completely unreactive.

ABO Blood-Group System↗

PubMed2000

Cell death during development of intercalated ducts in the rat submandibular gland.

Programmed cell death, or apoptosis, occurs during the development of many tissues and organs in almost all multicellular organisms. Although apoptosis of salivary gland cells has been demonstrated in several pathological conditions, the role of apoptosis in the postnatal development of the salivary glands is unknown. We have studied the development of the rat submandibular gland (SMG) during its transition from the perinatal stage to the mature adult stage. Terminal tubule or Type I cells, which synthesize the secretory protein SMG-C, are prominent in the perinatal acini and are believed to form the intercalated ducts of the adult gland. Between 25 days and 30 days after birth, the number of Type I cells and their SMG-C immunoreactivity markedly decreased. Apoptotic cells in association with the developing intercalated ducts were labeled with the Terminal Deoxyribonucleotidyl Transferase-Mediated dUTP Nick End Labeling (TUNEL) method. Between 25 and 40 days of age, from 50 to 80% of the apoptotic cells in cryostat sections of the SMG were closely associated with the intercalated ducts. Electron microscopy showed that the Type I cells became vacuolated, their secretory granules were reduced in size and number, and the amount of rough endoplasmic reticulum was decreased. Cellular debris resembling apoptotic bodies was phagocytosed by macrophages and adjacent intercalated duct cells. These observations suggest that the loss of Type I cells and reduction of SMG-C immunoreactivity during development of the intercalated ducts of the adult rat SMG is due, at least in part, to apoptosis.

Animals↗

PubMed1995

Arachidonic acid stimulates intracellular calcium mobilization and regulates protein synthesis, ATP levels, and mucin secretion in submandibular gland cells.

Earlier observations that arachidonic acid inhibited the synthesis of membrane inositol phospholipids in rat submandibular acinar cells prompted the present study on whether the fatty acid may also regulate other key physiological processes in the model. Arachidonate, at concentrations above 10 mumol/L, inhibited up to 97% protein synthesis in acinar cells. The acid also lowered cellular ATP levels to 25% of control values by a ouabain-insensitive mechanism. In endoplasmic reticulum-calcium studies in permeabilized cells, arachidonic acid stimulated the mobilization of up to 73% loaded ER-45Ca2+ to the cytosol, a much greater response than those caused by other calcium translocators, thapsigargin or inositol 1,4,5-trisphosphate. Additionally, arachidonate provoked the release of over 80% of total cell 45Ca2+ to the extracellular space in intact cells and stimulated mucin secretion in the submandibular model. The inhibitory effect of arachidonic acid on protein synthesis was duplicated by carbachol, thapsigargin, and BAPTA/AM, three agents that cause net efflux of ER-Ca2+ by different mechanisms. Furthermore, comparable with the arachidonate effect on ATP, carbachol and thapsigargin also significantly reduced cellular levels of the nucleotide. It is concluded that arachidonic acid acts as a regulator of central synthetic/secretory processes in mucous acinar cells of rat submandibular gland and suggested that at least some of its effects may be secondary to its calcium-mobilizing action.

Adenosine Triphosphate↗

PubMed1981

[Formation of a regeneration stimulus following after submandibular gland and liver injury in the presence of total sympathetic nervous system suppression].

Resection of the submandibular gland or liver in Wistar rats leads to the increased proliferation of the retinal epithelium 72 hours after operation. This phenomenon is not connected with post-traumatic hemorrhage. Preliminary total inhibition of the sympathoadrenal system by diphtheria toxin abolishes the proliferation stimulus to regeneration. Participation of catecholamines in post-traumatic cell proliferation is suggested.

Adrenal Medulla↗

PubMed1991

[Embryonal carcinoma of the submandibular gland. Apropos of a case].

The authors report a case of infantile embryonal carcinoma of the submandibular gland in a nine months old infant. The diagnosis was based on typical histopathological features, and positive reaction of tumor cells with alpha-foetoprotein. The patient was treated by wide surgical excision and chemotherapy. The clinical course was favourable two years later with normalization of serum alpha-foetoprotein levels and with no abnormality on the thoraco-abdomino-facial CT scan.

Humans↗