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Investigations of prejunctional alpha 2-adrenoceptors in rat atrium, vas deferens and submandibular gland.

We have examined the effects of a series of alpha 2-adrenoceptor antagonists on the stimulation-evoked release of tritium from rat atrium, vas deferens and submandibular gland pre-incubated with [3H]noradrenaline, and correlated these potencies with affinities for the alpha 2A-ligand binding site of human platelet and the alpha 2B-ligand binding site of rat kidney. The alpha 2B-selective adrenoceptor antagonists prazosin and ARC 239 showed significantly higher, and the alpha 2A-selective antagonist BRL 44408 showed significantly lower, potency in atrium than in vas deferens and submandibular gland. Yohimbine and BDF 8933 failed to distinguish between prejunctional alpha 2-adrenoceptors or between ligand binding sites. It is concluded that the prejunctional alpha 2-adrenoceptor of rat atrium resembles the alpha 2B-ligand binding site, and differs from the prejunctional alpha 2-adrenoceptors of rat vas deferens and submandibular gland, which resemble the alpha 2A-ligand binding site.

Adrenergic alpha-Antagonists↗

Submandibular gland aplasia and progressive dental caries: a case report.

When severe caries occurs in mandibular permanent incisor teeth, the clinician should consider the possibility of associated submandibular gland aplasia or salivary hypofunction. Early diagnosis of submandibular gland disease is essential, as operative problems involving restoration of mandibular incisor teeth are considerable. Furthermore, progressive severe dental caries can present a dilemma for the clinician in affected individuals, despite intensive preventive and restorative therapy. A case report describing severe progressive dental caries and enamel demineralization of the permanent mandibular incisor teeth in a young girl is presented. Further investigation revealed absence of functional bilateral submandibular salivary glands contributing to the rapid breakdown of the teeth despite intensive preventive measures.

Adolescent↗

Lectin histochemistry of submandibular glands following duct-ligation in mice and rats.

Lectin binding patterns of Con A, PNA, SBA, DBA, WGA, RCA-1 and UEA-1 were carried out in duct-ligated submandibular glands (SMGs) of rats that displayed acute degenerating changes. Lectin staining was also related to histologic changes. Proliferating epithelial cells which were probably derived from intercalated duct cells showed a strong SBA and WGA staining on the 3rd day. Duct-like and cystic structures appeared on the 7th day and staining by PNA, SBA, WGA, RCA-1 and Con A was described. In mice, lectin binding after duct ligation appeared similar to the rat. In the long-term observation of mice SMGs, acinar cell regeneration occurred between the 21st and 42nd days and they stained strongly for DBA.

Animals↗

Presence and effects of pituitary adenylate cyclase activating peptide in the submandibular gland of the ferret.

Pituitary adenylate cyclase activating peptide (PACAP), a recently described vasoactive intestinal peptide-like neuropeptide, was found to be present in neurons in the submandibular gland of the ferret, where PACAP-immunoreactive nerve fibers were distributed around blood vessels, acini and ducts. Most of the PACAP-immunoreactive fibres were distinct from those storing vasoactive intestinal peptide. PACAP occurs in tissues as PACAP1-38 and PACAP1-27. PACAP1-38 and PACAP1-27 but not PACAP16-38 displayed biological activity with about the same potency. They exerted vasodilator effects on the submandibular vasculature, which resulted in a greater fall in vascular resistance than an equimolar dose of vasoactive intestinal peptide. The vasodilator response was independent of muscarinic receptor activation. Neither vasoactive intestinal peptide nor PACAP alone evoked any flow of saliva. However, both vasoactive intestinal peptide and PACAP enhanced the fluid response to acetylcholine, and the flow of saliva as well as the output of protein in response to parasympathetic nerve stimulation, vasoactive intestinal peptide being more potent than PACAP. In vitro, protein was released from submandibular gland tissue in response to both vasoactive intestinal peptide and PACAP, vasoactive intestinal peptide being more potent than PACAP. PACAP (and vasoactive intestinal peptide) exerted its in vitro effect following adrenoceptor and muscarinic blockade and following degeneration of sympathetic nerves. Sympathetic denervation combined with parasympathetic preganglionic denervation resulted in supersensitivity to both vasoactive intestinal peptide and PACAP. The fact that PACAP and vasoactive intestinal peptide occur in different nerve fibre populations suggests different roles for the two peptides in the submandibular gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Transplantation of the autologous submandibular gland for most severe cases of keratoconjunctivitis sicca.

OBJECTIVE: This study aimed to examine the long-term qualitative and quantitative function of the secretion of transplanted autologous submandibular glands in patients with most severe keratoconjunctivitis sicca. DESIGN: The study design was clinical. PARTICIPANTS: The authors performed 26 operation in 22 patients. A complete ophthalmologic examination was performed in 16 eyes of 13 patients 1 week and 3 months and in 8 eyes of 8 patients 1 year after surgery. INTERVENTION: The submandibular gland was moved from its natural site into the temporal fossa. The glands supplying vessels were connected to the temporal artery and vein, and its secretory duct was implanted into the conjunctival fornix. MAIN OUTCOME MEASURES: Scintigraphy with Tc 99m Pertechnetate was used to document the graft vitality. Subjective symptoms and application frequency of artificial tears were recorded. Baseline as well as stimulated secretion and breakup time were measured and rose bengal staining and ocular ferning test were performed. In selected cases, the secretory product could be sampled for the detection of electrolytes, amylase, and secretory immunoglobulin A (SIgA). RESULTS: Scintigraphy showed vital gland tissue in 14 of 16 grafts at 3 months and 6 of 8 grafts at 1 year after surgery. Two of the 16 transplants were lost completely during the first 3 postoperative months, 1 because of an underlying autoimmunopolyendokrinopathy and the other because of an insufficient vascular anastomoses. In eyes with a vital transplant, baseline secretion and breakup time were increased significantly at 3 months and 1 year after surgery. Patients with a vital transplant reported a strong relief of symptoms and were able to stop taking artificial tear substitution at 1 year. Electrolytes showed a fluctuating concentration. A year after transplantation, the SIgA and amylase concentrations were more than ten times increased compared to normal tear values. CONCLUSION: Microvascular transferral of an autologous, paralytic submandibular gland results in a significant relief of subjective symptoms, a reduction of artificial tear applications, and an increase of baseline secretion over the first postoperative year. The composition and volume of the secretory product fluctuate, but high values of SIgA and amylase show an actively secreting graft. Although the authors' long-term experience still is limited, they believe that the procedure is a promising alternative approach for desperate dry eye conditions.

Amylases↗

Immunocytochemical localization of heparan sulphate proteoglycan in the rat submandibular gland.

Heparan sulphate proteoglycan is the predominant proteoglycan synthesized by the parenchymal cells of the rat submandibular gland. A polyclonal antibody was used to localize this proteoglycan in the adult rat submandibular gland. Localization was accomplished by indirect immunoperoxidase cytochemistry at the light and electron microscopic levels. Heparan sulphate proteoglycan was localized in a continuous, linear pattern in the lamina densa of the basement membrane surrounding all of the epithelial components of the gland as well as the basement membrane of the capillaries and small arterioles in the glandular stroma. In addition, heparan sulphate proteoglycan was seen in vesicles and pits along the acinar cell basal plasmalemma adjacent to the basement membrane and in the endoplasmic reticulum and Golgi apparatus of the acinar cells.

Animals↗

Sexual difference in kininase activity in the mouse submandibular gland.

A marked sexual difference in kininase activity was found in the adult mouse submandibular gland. The activity was over 3-fold higher in females than in males between 10 and 12 weeks of age. Castration of male mice increased kininase activity up to the level of females. Testosterone administration to castrated males restored enzyme activity to about the normal level. Moreover, testosterone administration to normal females decreased enzyme activity to about the level of normal male mice, while ovariectomy had no effect. These results suggest that kininase activity in the mouse submandibular gland is suppressively regulated by endogenous androgen.

Aging↗

Identification of mK1, a true tissue (glandular) kallikrein of mouse submandibular gland: tissue distribution and a comparison of kinin-releasing activity with other submandibular kallikreins.

The protein structure, kinin-releasing activity, and tissue distribution of four major proteinases of mouse submandibular gland (mK22, mK9, proteinase F, proteinase P) were studied. When compared with the deduced amino acid sequence of each member of the tissue (glandular) kallikrein gene family, the amino acid sequence of proteinase F determined (approximately 40% of the total) was found to agree completely with the deduced amino acid sequence of mKlk-1. The proteinase P sequence, on the other hand, agreed with that of the product of mKlk-13, mK13 (prorenin-converting enzyme). Proteinase F had the strongest kininogenase activity for both low-molecular-weight and high-molecular-weight kininogen, while mK22 had 1/6 and 1/50 the activity of proteinase F for the respective kininogen substrate. Kininogenase activities of mK9 and proteinase P were less than 1/100 of the activity of proteinase F for both substrates. Acting on the two kininogen substrates, kallikreins mK22, mK9, and proteinase F, but not proteinase P, specifically released bradykinin, suggesting that the former three kallikreins strictly recognized peptide sequences around bradykinin in these substrate molecules but proteinase P recognized several sites in these molecules. Significant amounts of proteinase F, but not mK22 and others, were present in the urine, pancreas and digestive organs, as well as in the salivary glands. The present results revealed that the former proteinase F is identical to mK1, tissue/renal kallikrein, and confirmed its characteristics as a true kallikrein on the basis of its kinin-releasing activity and tissue distribution.

Amino Acid Sequence↗

Nitric oxide-related vasodilator responses to parasympathetic stimulation of the submandibular gland in the cat.

1. The extent to which parasympathetic vasodilator responses, in the submandibular gland of the cat, depend upon release of nitric oxide related (NO chi) or endothelium-derived relaxing factor (EDRF) within the gland has been investigated in anesthetized cats given N omega-nitro-L-arginine methyl ester (L-NAME) which specifically blocks the synthesis of EDRF from arginine. 2. Close intra-arterial infusions of L-NAME (> or = 100 mg kg-1) produced a steady and significant rise in mean aortic pressure together with a steady increase in basal submandibular vascular resistance over the next 20-30 min, which persisted thereafter. 3. In cats pretreated with propranolol, to block beta-adrenoceptor-mediated vasodilatation, salivation and vasodilatation in response to stimulation of the chorda-lingual nerve were reduced but not abolished by L-NAME (> or = 100 mg kg-1, I.A.). Subsequent administration of atropine (> or = 1 mg kg-1 I.V.) completely suppressed the secretory response and virtually eliminated the vascular response. 4. In cats pretreated with atropine (> or = 1.0 mg kg-1 I.V.) administration of L-NAME (> or = 100 mg kg-1 I.A.) effectively suppressed the vasodilator response to chorda-lingual stimulation at 2 Hz continuously, or at 20 Hz for 1 s at 10 s intervals. 5. Administration of L-NAME (> or = 100 mg kg-1 I.A.) effectively suppressed the submandibular vasodilator response to infusions of VIP (10 and 20 ng I.A.) and significantly reduced, but did not abolish that to acetylcholine (100 ng min-1 I.A.). 6. These results provide further support for the view that both acetylcholine and vasoactive intestinal polypeptide-like immunoreactivity (VIP) are released from the postganglionic parasympathetic nerve terminals and produce effects on the blood vessels in submandibular glands of the cat. They also provide evidence for a direct vascular action of acetylcholine, independent of NO chi, but VIP appears to act indirectly via NO chi formation.

Animals↗

[Effects of TNM extension and histopathological type of the tumor on long-term survival rates of parotid and submandibular gland cancer].

The effects of TNM extension and histopathological type of the tumor on 5 and 10-year survival rates were analysed in 1,147 cases of parotid cancer and 271 cases of submandibular gland cancer which had been registered from 152 institutes throughout Japan since 1978. Advance of stage decreased the prognosis significantly, and the decrease was more pronounced in submandibular gland cancer. Facial paralysis also decreased the prognosis of parotid cancer significantly. The prognosis was also affected significantly by the histopathological type of the tumor. The 5-year survival rates of adenocarcinoma, epidermoid carcinoma and undifferentiated carcinoma were only about 30% in parotid cancer and about 20% in submandibular gland cancer. In treatment of salivary gland cancer, the therapeutic approach should be individualized in accordance with the tumor extension and its histopathological type. Improvement of accuracy in preoperative diagnosis of salivary gland cancer is of the utmost importance.

Adenocarcinoma↗

Salivary gland function after sialolithiasis: scintigraphic examination of submandibular glands with 99mTc-pertechnetate.

Scintigraphic evaluation of 13 cases of submandibular duct sialolithiasis was performed to determine glandular function and to estimate the justification for sialoadenectomy. Twenty-two per cent of these glands showed no function despite sialolithectomy, which suggests that it would be reasonable to excise submandibular salivary glands that have no recovery of function. However, the remaining 78% of the glands showed varying degrees of recovery of function, indicating that sialolithectomy should be done first, followed by 99mTc-pertechnetate scintigraphic examination to determine the necessity of further sialoadenectomy.

Adolescent↗

Pathobiology of salivary glands. IV. Histogenetic concepts and cycling cells in human parotid and submandibular glands cultured in floating collagen gels.

Localization of cells with proliferative capacity in human major salivary glands lacks extensive study. Minced fragments of human parotid (n = 3) and submandibular (n = 3) glands embedded in a floating collagen gel matrix and cultured for up to 28 days allowed maintenance of the three-dimensional relationship of the various cell types in these glands. Immunocytochemistry and electron microscopy of a time-dependent series of cultured gland fragments showed gradual cytologic modification of acinar cells so that acini became duct-like but also established that even after 28 days of culture certain cellular features allowed continued identification of acinar cells. Serial section immunostaining for amylase, cytokeratins, and proliferating cell nuclear antigen (a specific marker for cycling cells) revealed that acinar, intercalated duct, and excretory duct (both basal and luminal) cells are all capable of entering the cell cycle. At day 5 of culture, the number of cycling cells increased 16-fold in the parotid gland and 9-fold in the submandibular gland over that in the respective in situ gland. In this in vitro system, which perhaps simulates regenerative processes in human salivary glands, none of the samples showed cycling cells localized only to segments of intercalated duct or the basal cells of excretory duct as suggested by current histogenetic concepts.

Cell Adhesion↗

Atrial natriuretic peptide stimulates submandibular gland synthesis and secretion of cGMP.

Binding of atrial natriuretic peptide (ANP) to rat submandibular gland and its effect on guanosine 3',5'-cyclic monophosphate (cGMP) formation and salivary secretion were investigated. Membranes rapidly and specifically bound 125I-ANP. Binding was inhibited by unlabeled ANP (IC50 approximately 1.6 nM), but not by atriopeptin I, other COOH- and NH2-terminal deleted ANP fragments, or agents such as pilocarpine or substance P. Scatchard analysis revealed a single class of high-affinity sites (dissociation constant 0.74 +/- 0.25 nM; maximal binding capacity 20.5 +/- 6.3 pmol/mg protein). Intravenous infusion of ANP with pilocarpine caused a significant dose-dependent increase in the levels of cGMP detected in plasma and saliva. Because salivary cGMP may have originated in plasma, the effect of ANP on cGMP formation was evaluated in dispersed cells. ANP evoked a concentration-dependent increase in both cGMP synthesis and secretion (EC50 approximately 1.7 x 10(-8) M). The atrial peptide did affect basal or l-isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate synthesis in dispersed cells. When infused by itself and/or with pilocarpine, ANP did not alter the rate of spontaneous or pilocarpine-induced salivary flow, secretion of chloride, or protein release. The data demonstrate the presence of guanylate cyclase-coupled ANP receptors in submandibular gland; the atrial peptide, however, does not exert an effect of the secretory function of the gland.

Animals↗

Histological observation of the submandibular gland with special reference to the focal lymphocytic infiltration.

Focal lymphocytic infiltration of the submandibular gland was investigated on the autopsy cases. The materials examined were 340 cases without the collagen diseases and 28 cases with collagen diseases. Of the 28 cases with collagen diseases, 20 were systemic lupus erythematosus, 2 with the coexistence of systemic, lupus erythematosus and Sjögren's syndrome, 4 with rheumatoid arthritis and 2 with progressive systemic sclerosis. Among the cases without the collagen diseases, the focal lymphocytic infiltration was seen in 154 cases (74%) of 209 males and in 94 cases (71%) of 131 females. All 28 cases with collagen diseases had a focal lymphocytic infiltration. The incidence of grade 3 or severe infiltration was 4% in the males and 14% in the females in the cases without the collagen diseases, 65% in the 20 cases with systemic lupus erythematosus, 50% in the 4 cases with rheumatoid arthritis and 50% in the 2 cases with progressive systemic sclerosis. No cases of very severe infiltration were found, which were seen in the classical Sjögren's syndrome, in both cases with and without the collagen diseases. Hyperplastic change in the ductal cells, which can be called an epimyoepithelial island, was found in 23% of the cases with collagen diseases. These observations suggest that the focal lymphocytic infiltrations is a focal sign of the immunologic disorder of the submandibular gland in the collagen disease.

Adolescent↗

Mouse submandibular gland salivary apomucin contains repeated N-glycosylation sites.

A cDNA clone encoding mouse submandibular gland salivary mucin apoprotein was isolated and characterized. The mucin cDNA encodes a protein of 273 amino acids with a calculated molecular weight of 29,606. This apomucin is approximately 60% Thr, Ser, and Pro, and has a pI of 11.25. In addition to the signal sequence, the apomucin can be divided into four structural domains. The first of these contains over 30% Thr, Ser, and Pro, but only a few probable O-glycosylation sites. The second domain contains 10 repeats, each 9 or 13 amino acids in length, with Thr representing more than 50% of the amino acids, while Ser accounts for only 2%. Each repeat begins with a putative N-glycosylation site; hence this domain likely contains both N- and O-linked oligosaccharides. The third domain lacks a repeat motif, but is rich in both Thr and Ser, and therefore is potentially highly O-glycosylated. The final domain is composed mainly of basic and non-polar amino acids and does not contain Cys. This mucin shows considerable homology with the rat submandibular salivary mucin, but little overall homology with other mucins. In situ hybridization verifies that the mucin transcript is localized primarily in the acinar cells of the submandibular gland.

Amino Acid Sequence↗

Alteration of the submandibular glands of female mice during pregnancy and lactation. A histological, histometric and histochemical study.

The submandibular glands of mice show "masculinization" during pregnancy and lactation. In this work involving morphological, morphometric and histochemical analyses we observed an increase in the volume fraction and area of the granular ducts and the apical granulation of their cells. The maximum response to the masculinization occurred on the 15th day of pregnancy. From this day on a decrease in the volume fraction of the granular ducts starts, even though the gland keeps the "masculine pattern" throughout the end of the lactation phase. Our observations support the intermodulation between striated and granular ducts. In our opinion, the "masculinization" process of the submandibular gland is related to the progesterone increase which takes place during pregnancy; its maintenance during lactation is also connected to prolactin.

Animals↗