Effect of nitrendipine, a calcium antagonist, on cell volume in rat salivary glands after isoproterenol stimulation.

Four days of isoproterenol injections induced a marked enlargement of the rat parotid and submandibular glands reflected in significant increases in the absolute and relative wet and dry weight of the glands. The enlargement in parotid gland was attributable at least in part to cellular hypertrophy inasmuch as the average volume per cell of acinar cells increased. In contrast, the average volume of acinar cells in the submandibular gland was decreased as compared to that of control. It is likely that hyperplasia in both groups accounts in part for the enlargement. The slow calcium channel is unlikely involved in the isoproterenol-induced stimulation of the gland, inasmuch as the calcium channel antagonist did not modify the enlargement of the parotid or submandibular glands.     

Effect of T-lymphocytes on the cellular proliferation of the salivary glands in rats and mice exposed to isoproterenol

It has been shown that in the course of isoproterenol induction of cell proliferation of rat and mouse salivary glands, there takes place formation of T lymphocytes that stimulate and inhibit proliferation of the gland cells. In the absence of T lymphocytes isoproterenol does not induce cell proliferation. It has been demonstrated in mice that lymphocytes that stimulate cell proliferation of the salivary glands belong to Ly 1+ T lymphocytes whereas those inhibiting proliferation to Ly 2+ T lymphocytes. The former ones are formed and proliferate before commencement of glandular cell proliferation, and the latter ones concurrently with the development of cell proliferation of the salivary glands. The mechanisms described may point to the existence of a special system of T lymphocytes, that is not identical to the immune system, with this special system playing a definite role in the maintenance of the proliferative homeostasis of host tissues.     

Induction of proline-rich glycoprotein synthesis in mouse salivary glands by isoproterenol and by tannins

Glycoproteins which contain about 45 mol% proline were dramatically induced in mouse parotid and submandibular glands by isoproterenol treatment, but these unusual proteins were not detected in control animals. These acid-soluble substances were obtained by extracting tissues with 10% trichloroacetic acid, as reported previously for isolating proline-rich proteins from rat submandibular glands (Mehansho, H., and Carlson, D.M. (1983) J. Biol. Chem. 258, 6616-6620). Three major proline-rich glycoproteins were induced in parotid glands with apparent molecular weights of 66,000 (GP-66p), 45,000 (GP-45p), and 27,000 (GP-27p), whereas only one such protein was expressed by the submandibular glands (66,000 (GP-66sm]. Both GP-66p and GP-66sm contained about 19% carbohydrate with the following molar ratios, respectively; GalNAc, 1.0, 1.0; Gal, 1.6, 2.3; GlcNAc, 0.8, 1.1; sialic acid, 0.9, 1.9. The peptide chains of GP-66p and GP-66sm appear to be identical by amino acid compositions, glycopeptide analysis, and preliminary amino acid sequencing data. Northern blot analysis of RNAs from parotid glands of normal and isoproterenol-treated rats, probed with a 32P-labeled proline-rich protein cDNA, confirmed that control animals were devoid of mRNAs encoding these proteins and that isoproterenol treatment dramatically induced expression of these genes. Feeding sorghum high in tannins caused changes in the parotid glands similar to those observed upon isoproterenol treatment, as noted earlier with rats (Mehansho, H., Hagerman, A., Clements, S., Butler, L., Rogler, J., and Carlson, D.M. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 3948-3952). These glycoproteins have high affinities for tannins as demonstrated by competitive binding curves.     

Increased secretion of salivary glands produced by facial vibrotactile stimulation

Patients with low-back pain can be evaluated immediately by means of an electrical tool that produces bony vibration to the lumbar spinal processes (Yrjama M, Vanharanta H. Bony vibrotactile stimulation: A new, non-invasive method for examining intradiscal pain. European Spine Journal 1994;3:233–235). In the rehabilitation of masticatory disturbance and dysphagia, an electric toothbrush is commonly used as an oral motor exercise tool for the facilitation of blood flow and metabolism in the orofacial region in Japanese hospitals. However, subjects receiving vibration in the facial regions reported increased salivary secretion. We attempted to develop an oral motor exercise apparatus modified by a headphone headset that was fixed and could be used for extended periods. The vibration apparatus of the heating conductor is protected by the polyethyle methacrylate (dental mucosa protective material), and electric motors for vibration control of the PWM circuit. We examined the amount of salivation during vibration stimuli on the bilateral masseter muscle belly, using a cotton roll positioned at the opening of the secretory duct for 3 min. Although the quantity of salivation in each subject showed various and large fluctuations in the right and left sides of the parotid and submandibular and sublingual glands, one or more of the salivary glands were effectively stimulated by 89 Hz vibration. The reported apparatus will be useful as an additional method in orofacial rehabilitation.     

Regulation of phosphofructokinase-1 on submandibular salivary glands of rats after isoproterenol administration

The purpose of this investigation was to study the effect of isoproterenol (IPR) treatment on the regulation of phosphofructokinase-1 of submandibular salivary glands of rats. The animals were divided into control and experimental groups. In the first set of experiments, the rats received 5 mg of IPR/kg b.w. and were sacrificed at 24 hours after 1, 2, 3 and 4 doses. The content of fructose-2,6-bisphosphate (Fru-2,6-P(2)) and the activity of 6-phosphofructo-2-kinase (PFK-2) (active and total) were determined. The Fru-2,6-P(2) content was found to be reduced and the activity of PFK-2 (active and total) showed differences from the control. The active/total ratio, was higher for the group of one dose sacrificed 12 hours after the agonist injection as compared to the control. In the other groups, there were reductions which varied from 25 to 33%. In the second set of the experiment, the animals were injected with 23.0 mg of IPR/kg b.w. and were sacrificed from 5 up to 720 minutes after the administration of the agonist. After the sacrifice, salivary gland samples were analyzed for Fru-2,6-P(2). Again, a reduction in the metabolite content was observed. Using beta and alpha receptor blockers, it was found that both inhibited only partially the effect of IPR. The purification of PFK-1 up to homogeneity, from submandibular glands of rats which received 5 mg of IPR/mg b.w. as well as from the control, was performed and the Km and state of phosphorylation were determined. Rats from the group sacrificed 12 hours after the injection of the agonist showed the lowest Km for Fru-6-P. Animals which received 3 doses of IPR showed the highest phosphate content/mol of enzyme. Experiments of dephosphorylation of the purified PFK-1 from this latter group revealed that the presence of the phosphate groups influence the kinetic properties of the enzyme.     

Protein and DNA levels in the submandibular salivary glands of isoproterenol stimulated mice

The DNA and soluble and sedimental protein levels were studied in isoproterenol stimulated mouse submandibular salivary glands over a period of 200 h. Hypertrophy, the predominant cellular phenomenon following chronic isoproterenol treatment, was associated with a marked elevation of 14C-leucine incorporation into the buffer soluble protein fraction and a less pronounced isotope incorporation into the sedimental sub-cellular fraction as well as continued DNA synthesis. These findings are contrary to the accepted definitions of hypertrophy which preclude continued DNA synthesis. A suggestion is made, therefore, that in the system used the polyploidy associated with the hypertrophy involves.     

Effect of lithium on secretory factors and growth stimulation by bombesin in rat pancreas and salivary glands

Lithium, a drug of choice in bipolar affective disorders, also affects the metabolism and cell proliferation in a diverse array of organisms. In this study, we investigated the effect of lithium on bombesin-mediated function in excretion and growth of the pancreas and the salivary glands. The weight, protein content, amylase concentration and salivary flow rate of the pancreas, parotid and the submandibular glands were determined in male Wistar rats after consumption of either water or lithium chloride (600 mg/l) for 14 days and each group received s.c. injection of either saline or bombesin (10 microg/kg) during the last 4 days of experiment. Our results revealed that administration of bombesin in lithium-treated group not only suppressed pancreas and parotid weight augmentation due to bombesin, but also significantly decreased pancreas growth. Chronic lithium consumption significantly inhibited the protein content augmentation due to bombesin in the salivary glands. Getting bombesin, as well as saline in lithium-treated group, resulted in notable decrease in salivary protein content. Protein content of pancreatic gland increased considerably in the bombesin-injected groups either treated with saline or lithium. In conclusion, the stimulatory effect of bombesin on the growth and protein content of the pancreas and the salivary gland was inhibited by lithium. Lithium seems to be a potent inhibitor of growth factors induced by bombesin probably through inhibiting phosphatidylinositol 4,5,bisphosphate hydrolysis.     

Induction of proline-rich proteins in hamster salivary glands by isoproterenol treatment and an unusual growth inhibition by tannins

Treatment of hamsters with the beta-agonist isoproterenol caused a dramatic increase in a series of unusual proteins in the parotid and submandibular glands. These proteins are acid soluble and they contain high amounts (mol%) of glutamate plus glutamine (30-35), proline (23-30), and glycine (12-25). Three proteins (HP45, HP43a, and HP43b) were isolated from trichloroacetic acid extracts of parotid glands of isoproterenol-treated hamsters. The basic protein (HP45) was not retained by DEAE-cellulose and did not contain phosphate or carbohydrate. Two acidic proteins (HP43a and HP43b) had the same apparent molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but these were separated by DEAE-cellulose chromatography. HP43a and HP43b contained 4.3 and 5.7 phosphate residues/mol of protein, respectively. Levels of mRNAs encoding this series of proteins showed striking increases following isoproterenol treatment as determined by cell-free translations and Northern analysis. Feeding tannins to rats and mice mimicks the effects of isoproterenol treatment on the parotid gland (Mehansho, H., Hagerman, A., Clements, S., Butler, L., Rogler, J., and Carlson, D.M. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 3948-3952; Mehansho, H., Clements, S., Sheares, B. T., Smith, S., and Carlson, D. M. (1985) J. Biol. Chem. 260, 4418-4423]. However, hamsters on a high tannin diet (2%) did not respond like rats and mice and instead displayed an unusual growth inhibition. Weanling hamsters maintained on a 2% tannin diet initially lost weight for 3 days and then failed to gain weight for up to 6 months when kept on this diet. Essentially a normal growth rate was observed when the tannin-fed hamsters were switched to a normal diet.     

Changes in the polypeptide composition of mouse parotid glands after stimulation of secretion and DNA synthesis by isoproterenol

The polypeptide composition of mouse parotid glands has been analysed by unidimensional SDS-polyacrylamide slab gel electrophoresis and Coomassie blue staining after isoproterenol stimulation of secretion and DNA synthesis. Two polypeptides (polypeptides A and B) are lost within 2 h and their restoration in the glands occurs according to a chronology which is identical to that of the alpha-amylase activity. On the other hand, five clearly defined new bands appear consistently during the late prereplicative period of isoproterenol-stimulated mouse parotid acinar cells (polypeptides C, D, E, F and G). These new polypeptides are induced by doses of isoproterenol which provoke secretion and DNA synthesis, but not by doses which provoke only secretion. Although no function has been assigned to any of the above-described polypeptides, a relation between polypeptides A and B and secretion and between polypeptides C, D, E, F and G and the proliferative response is suggested.     

Compensatory function of submandibular salivary glands in diabetes and prospects for stimulating them with isoproterenol

A brief review is presented of experimental studies conducted over several years (1970s-1990s) on the incretory potential of salivary glands, specifically on their role in the maintenance of carbohydrate homeostasis; a review is also presented of data on the stimulation of this potential by isoproterenol, a beta-adrenergic agonist.