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Submandibular gland acinar cells express multiple alpha1-adrenoceptor subtypes.

We evaluated an acinar cell line (SMG-C10) cloned from rat submandibular glands as a possible model for alpha(1)-adrenoceptor regulation of submandibular function. alpha(1)-Adrenoceptors are subdivided into three subtypes called alpha(1A), alpha(1B), and alpha(1D), which can be distinguished from one another by their differential affinity values for subtype-selective alpha(1)-adrenoceptor antagonists. Thus, alpha(1)-adrenoceptor subtypes in SMG-C10 cells were characterized with reverse transcription-polymerase chain reaction (RT-PCR) and [(3)H]prazosin binding in side-by-side experiments with native submandibular glands. RT-PCR identified mRNAs for alpha(1A)-, alpha(1B)-, and alpha(1D)-adrenoceptors in SMG-C10 cells and submandibular glands. The inhibition of [(3)H]prazosin binding by 5-methylurapidil (alpha(1A)-selective) was biphasic and fit best to a two-site binding model with 40 +/- 8% high (K(iH))- and 60 +/- 10% low (K(iL))-affinity binding sites in SMG-C10 cells, and 76% high- and 24% low-affinity binding sites in submandibular glands. Respective K(iH) and K(iL) values for 5-methylurapidil were 1.9 +/- 0.4 and 100 +/- 30 nM in SMG-C10 cells and 3.2 +/- 0.8 and 170 +/- 20 nM in submandibular glands. BMY-7378 [8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride (alpha(1D)-selective)] bound with low affinity in SMG-C10 cells and submandibular glands with K(i) values of 81 +/- 20 and 110 +/- 20 nM, respectively. Chloroethylclondine, an irreversible alkylating agent selective for alpha(1B) adrenoceptors, reduced the density of [(3)H]prazosin binding sites by 42 and 26% in SMG-C10 and submandibular membranes, respectively. Thus, SMG-C10 cells and submandibular glands are similar in expressing receptor protein for alpha(1A)- and alpha(1B)-adrenoceptor subtypes, establishing SMG-C10 cells as a potential model for alpha(1)-adrenoceptor-mediated secretion.

Adrenergic alpha-Antagonists↗

In vitro secretion of immunoreactive tonin from dispersed rat submandibular gland cells.

Dispersed cells from the submandibular gland of the male rat were prepared by collagenase treatment to study the mechanism by which immunoreactive tonin is secreted in vitro. Norepinephrine, epinephrine, and phenylephrine stimulated tonin release, an effect that was inhibited by phentolamine but not by propranolol, whereas isoproterenol, carbachol, histamine, and serotonin did not stimulate tonin release. The stimulatory effect elicited by alpha-adrenergic agonists was inhibited by both removal of Ca2+ from the medium and addition of diltiazem and nifedipine, both selective calcium channel blockers. The divalent cation ionophore A23187 stimulated tonin release in the presence of Ca2+, but not in the presence of Mg2+. Dibutyryl cyclic adenosine 3',5'-monophosphate, methylisobutylxanthine, angiotensin II, and vasoactive intestinal peptide had no effect on tonin release. The apparent molecular size of immunoreactive tonin released into the medium under basal and norepinephrine-stimulated conditions was similar to that of standard tonin by gel exclusion chromatography. These data suggest that the in vitro secretion of immunoreactive tonin from rat submandibular gland is initiated by activation of alpha-adrenergic receptors and apparently involves a mechanism dependent not on cyclic adenosine 3',5'-monophosphate, but on the influx of extracellular Ca2+.

Animals↗

Morbidity associated with removal of the submandibular gland.

Postoperative complications in 206 submandibular gland excisions, excluding those resulting from benign or malignant tumours, carried out during a 15-year period were reviewed. Most patients (62%) had sialolithiasis. Coexistence of sialolithiasis and nephrolithiasis was documented in 5.5% of cases. Early postoperative complications (particularly infection) developed in 14.6% of the cases, whereas late complications appeared in 25.3% of the cases (residual inflammation in Wharton's duct 7.3%). Neurological complications were observed in 16% of the cases. In 7 cases (3.4%) several nerves were involved and almost always the hypoglossal nerve. In 37.4% of the cases, these lesions resolved spontaneously in a mean period of 4 months. In those cases with a permanent neurological deficit, the facial nerve was the most often affected (7.7%) followed by the hypoglossal (2.9%) and the lingual nerve (1.4%). A single case of gustatory sweating (Frey's) syndrome was observed.

Adult↗

Constitutive secretion of kallikreins in vivo from rat submandibular glands.

In parasympathetic saliva from rat submandibular glands the relative proportions of the various tissue kallikreins differ from those in sympathetic saliva. Kallikreins in sympathetic saliva arise from exocytosis of prepackaged granules in granular tubules, so the kallikreins in parasympathetic saliva must come from a non-granular pool, and are likely to be secreted through a constitutive vesicular route. During periods devoid of stimulation in anaesthetised rats, the kallikreins have been found to accumulate progressively in glandular lumina in parasympathetic-like proportions. As this transport of kallikrein into lumina occurs continuously in vivo, independently of any stimulation or any secretion of fluid, it must arise by constitutive vesicular secretion. During parasympathetic stimulation, the kallikreins are secreted into the saliva at a greater rate than in the resting state but their proportions remain the same and the means by which this increase occurs is open to debate. Constitutively secreted true tissue kallikrein (rK1) has been found to have a different molecular form from that in secretory granules. The submandibular glands also contribute to the kallikreins normally circulating in the blood. Serum levels of kallikrein increased equally during either parasympathetic or sympathetic stimulation and were independent of the amounts secreted into the saliva, so are likely to have arisen from constitutive secretion via the basal sides of the cells, morphological evidence for which has been found in the mouse (Penschow & Coghlan, 1993).

Animals↗

Intraoral removal of the submandibular gland: a new surgical approach.

The transcervical procedure used for treating sialolithiasis in the submandibular gland has been generally accepted by head and neck surgeons. However, several clinical problems after surgery through the transcervical approach have been described. We introduce a new surgical approach for excision of the submandibular gland indicated in the chronically inflamed salivary gland with or without calculus and benign mixed tumor of the submandibular gland. Thirty-one cases of submandibular gland excision through the intraoral approach were reviewed, analyzing surgical technique and morbidity. Early postoperative discomforts developed, such as a temporary lack of function of lingual nerve and a temporary limitation of tongue movement, but recovery was within a short period of time in all patients involved. No symptomatic late complications appeared, such as residual inflammation of Wharton's duct and neurologic sequelae. We suggest that this approach can be extended to the excision of the submandibular gland as an alternative to the transcervical approach. The major advantages of this approach are the avoidance of an external scar and injury to the marginal mandibular nerve or the hypoglossal nerve.

Adolescent↗

Rat submandibular gland kallikreins: purification and cellular localization.

1 Four submandibular gland kallikreins (E.C.3.4.21.8) were isolated by chromatography on DEAE-Sephadex A-50 and hydroxyapatite, followed by gel filtration and electrofocusing. The pI values were 3.87, 3.96, 4.07 and 4.16, and a common molecular weight of 34,000 was found. 2 The kallikreins were localized by direct immunofluorescence with an antibody to rat urinary kallikrein, to the granular tubules, striated duct cells and some main duct cells in the submandibular gland, and to striated duct cells in the sublingual gland. Kallikrein was not found in acini and stroma. 3 Several non-kallikrein esterases present in the submandibular gland reacted with the antibody to rat urinary kallikrein. The antibody was made monospecific for kallikrein by absorption with the crossreacting esterases. 4 We suggest that kallikrein is produced in striated duct cells. Granular tubules, which are differentiated from striated duct cells, have preserved the ability to produce kallikrein. These cells also store large quantities of kallikrein.

Animals↗

Prediction of prognosis in peripheral facial nerve paralysis using submandibular gland scintigraphy.

UNLABELLED: In this study, we evaluated the ability of submandibular gland scintigraphy to predict the prognosis of peripheral facial nerve paralysis. METHODS: Submandibular gland scintigraphy was performed in 78 patients with acute peripheral facial nerve paralysis. After injection of 180-370 MBq [99mTc]pertechnetate, serial 1-min images were acquired for 25 min. At 15 min after injection of radionuclide, ascorbic acid was administered intraorally to stimulate salivary secretion. Regions of interest were set manually on both submandibular glands, and time-activity curves were generated. The ratios of peak count density (PCR) and washout (WR) of the affected side to the normal side were calculated. Parameters of > or = 0.8 suggested normal affected submandibular function and indicated a good prognosis. RESULTS: Complete recovery of facial nerve paralysis was observed in 52 of 78 patients. The sensitivity, specificity and accuracy of PCR for a good prognosis were 79%, 50% and 69%, and those of WR were 85%, 77% and 82%, respectively. Positive and negative predictive values for a good prognosis were 76% and 54% in PCR and 88% and 71% in WR, respectively. When WR obtained within 14 days of the onset was used, positive and negative predictive values for a good prognosis were 94% and 73%, respectively. None of the eight patients who had values of <0.8 for both parameters within 14 days of the onset recovered completely. CONCLUSION: Submandibular gland scintigraphy can serve as a reliable indicator to predict the prognosis of acute peripheral facial nerve paralysis in its early symptomatic period.

Acute Disease↗

Cytochemical detection of endogenous peroxidase in the acinar cells of the hamster submandibular gland.

The presence of endogenous peroxidase activity in the hamster submandibular gland was investigated cytochemically by light and electron microscopy using diaminobenzidine methods. After fixation of tissue with 2% paraformaldehyde-2.5% glutaraldehyde and incubation in a DAB reaction medium containing 0.01% H2O2, the peroxidase reaction product was localized in the nuclear envelope, the cisternae of the endoplasmic reticulum, secretory granules and the Golgi apparatus in both the acinar and granular duct cells of the submandibular gland. This is in contrast to earlier investigators who failed to detect peroxidase activity in acinar cells of the hamster submandibular gland and reported that peroxidase is localized only in the granular duct cells. The discrepancy may be caused by differences in experimental procedures. It is suggested that fixation of tissue with a high concentration of glutaraldehyde and incubation in a DAB reaction medium containing a high concentration of H2O2 inhibits the peroxidase activity of acinar cells in the hamster submandibular gland.

3,3'-Diaminobenzidine↗

Tumors of the submandibular gland: clinicopathologic analysis of 23 patients.

PURPOSE: Tumors of the submandibular gland are rare, comprising less than 2% of head and neck neoplasia. Both benign and malignant lesions show a mild symptomatology, resulting in late presentation and in advanced stage of disease. The purpose of this article was to report our experience in treating submandibular gland neoplasia during the last 10 years. PATIENTS AND METHODS: The medical records of all patients with histologically confirmed epithelial tumors of the submandibular gland were retrospectively reviewed. This review found 23 patients with 9 benign and 14 malignant tumors. The collection of data included demographic data, diagnostic procedures, operative and pathology reports, complications, additional treatment, and follow-up. RESULTS: There were 10 men and 13 women with a mean age of 60 years. Pleomorphic adenoma was the most frequently encountered benign tumor; adenocarcinoma and adenoid cystic carcinoma had an equal presentation in the malignant group of patients. Eleven of the 14 patients with malignant tumors presented in advanced stages of disease (stage III and IV). Surgery was the sole treatment for the benign tumors. There were no recurrences. In the majority of cases, patients with malignant tumors were treated with surgery and postoperative radiotherapy. Eight patients died during the follow-up period, giving a mortality rate of 61.5%. CONCLUSION: Benign submandibular gland tumors manifest a mild course of disease, and local excision along with the gland is a safe and effective method of treatment. Malignant tumors have a poor symptomatology that results in late diagnosis. Radical surgery and postoperative radiotherapy is the treatment of choice. Prognosis depends on the histopathology and biologic behavior of the specific type of malignant tumor.

Adenocarcinoma↗

Apoptosis and proliferation of myoepithelial cells in atrophic rat submandibular glands.

This study was designed to determine whether apoptosis and proliferation of myoepithelial cells occur in atrophic rat submandibular glands. The excretory duct of the right submandibular gland was doubly ligated with metal clips. The atrophic right submandibular glands removed after 1-28 days of duct ligation were investigated using immunohistochemical double staining for actin as a marker for myoepithelial cells and proliferating cell nuclear antigen (PCNA) as a marker for proliferating cells, double staining for actin immunohistochemistry, nick end-labeling (TUNEL) as a marker for apoptotic cells, and transmission electron microscopy (TEM). A few PCNA- and no TUNEL-positive myoepithelial cells were found in the control submandibular glands taken from animals with no operation. In the experimental glands, PCNA-positive myoepithelial cells were common 2 and 3 days after duct ligation and then decreased in number. TUNEL-positive myoepithelial cells appeared at 2 days and were observed most frequently at 5 days. Apoptotic myoepithelial cells were also identified by TEM. These observations suggest that both apoptosis and proliferation of myoepithelial cells occur, especially in the early phase of atrophy, in the rat submandibular gland.

Actins↗

Histopathology of submandibular glands removed for sialolithiasis.

We reviewed the clinical history of 48 consecutive patients who underwent submandibular gland removal for radiologically proven sialolithiasis. The specimens were examined by a pathologist blinded to the clinical data. A histopathologic classification into I of 3 grades was established by evaluating the degrees of atrophy, fibrosis, and inflammation. A correlation between the clinical and pathological variables was sought in order to define clinical variables that would predict abnormal submandibular glands that required extirpation. A significant percentage of the submandibular glands exhibited normal histologic findings. The patients with normal submandibular glands had a clinical evolution similar to that of other patients with severely damaged glands. The only clinical variable that correlated with increased histopathologic alteration was the patient's age. In view of the newly available diagnostic and therapeutic techniques for sialolithiasis, a conservative attitude to submandibular gland resection appears justified.

Adult↗

A case report of coexistence of a sialolith and an adenoid cystic carcinoma in the submandibular gland.

The occurrence of sialoliths in the submandibular gland is 80% due to the specific anatomy of both the gland and its duct. The diagnosis is rather easy because of the obvious clinical signs of the entity. Imaging studies are always necessary in order to treat the patient as effectively as possible. The stones do not tend to occur within the gland as frequently as in the respective duct. The coexistence of sialoliths and malignant tumors is extremely rare. A 70-year-old woman with intraparenchymal stone was operated in our ENT department. In addition to the sialolith the pathological examination revealed the existence of an adenoid cystic carcinoma (ACC), that extended to the neighboring skeletal muscle. This is the reason why we believe it would be useful to report this case of a large stone (14 mm in diameter) located in the submandibular gland coexisting with ACC. This case report is a very good example illustrating that all available means should be used prior to reaching a conclusion and making a health professional decision.

Aged↗

Submandibular glands: novel structures participating in thermoregulatory responses.

Since submandibular glands participate in the regulation of cardiovascular and immunological responses to bacterial endotoxin, we examined their role as modulators of endotoxin-induced fever. Core body temperatures were measured by telemetry in rats that had either a sham operation or a sialadenectomy 1 week previously and that were maintained at 23-24 degrees C. The sialadenectomized rats showed a circadian variation in body temperature similar to sham-operated rats, although their daytime body temperature was 0.24 +/- 0.01 degree C lower. The fever elicited by intraperitoneal injection of Escherichia coli endotoxin was biphasic, with an initial phase occurring between 2 and 3 h, and a broader second phase peaking between 4 and 8 h after endotoxin injection. The initial fever was similar in the two groups of rats, but the second phase of fever was significantly higher by 0.28 +/- 0.09 and 0.26 +/- 0.07 degree C in sialadenectomized rats receiving 50 or 150 micrograms/kg of endotoxin, respectively. Intravenous treatment with a novel peptide, submandibular gland peptide-T (SGP-T; 100 micrograms/kg), 30 min before endotoxin injection did not affect the early fever response, but significantly suppressed by 0.37 +/- 0.10 degrees C the late-phase fever provoked by 150 micrograms/kg of endotoxin. These results suggest that the submandibular glands modulate thermogenic responses to inflammatory stimuli possibly through the endocrine release of hormones, such as SGP-T.

Animals↗