In order to understand the functional morphology of mucin secretion, it is vital to appreciate what occurs during specimen preparation. The cells were examined using epifluorescence microscopy, utilizing standard filter sets to visualize rhodamine and fluorescein fluorochromes. It is concluded that in the gastrointestinal tract of the rat the colon and the cecum are more suitable locations for the mucoadhesion than the stomach and the jejunum because: 1 their mucus turnover is lower, 2 their sensitivity to mucus secretory stimulus is lower, and 3 their Polycarbophil adherence properties are stronger. In some tissues such as the chicken trachea, calcium is co-secreted with mucus. The cardiac and pyloric regions were richer with mucins than the fundic region. Verdugo used video enhanced microscopy to examine exocytosis of rabbit tracheal mucous cells and recorded the dimension of the mucous spherules at millisecond intervals.
On day 68 a final injection of 50 µg of mucin in incomplete adjuvant was given and after 10 days 20 ml of serum was collected and stored at —20°C. The intracellular events involved in mucus secretion, including the signal transduction pathways involved, have begun to be explored. The proportion of the larger subunit decreased in the order of cardiac, fundic and pyloric mucins, as 100, 61. In particular, any model must explain the intracellular packaging and the kinetics of release of these large, heavily charged species. Threonine and proline content decreased in the order of cardiac, fundic and pyloric mucin.
Received on May 8, 1999; revised on July 26, 1999; accepted on July 27, 1999. The effect of carbachol on mucus secretion was profound and dose dependent in the stomach, and less profound, although still dose dependent, in the proximal jejunum. Gallbladder bile from a mongrel dog was obtained during surgery by aspiration of the gallbladder by needle puncture and frozen at —20°C. It is conceivable that alkali secretion by the esophagus and duodenum plays a far greater role in protection against the smaller quantities of luminal acid found in these organs than in the stomach where luminal acidity is consistently higher and capable of overwhelming the mucus pH gradient. Mucous is used as an adjective to indicate relatedness to mucus or mucin, such as in mucous secretory granules, mucous secretory cells, or mucous glycoprotein. To maintain electrical neutrality, the negative charges of mucins inside the granule must be neutralized or shielded. Ongoing studies address the feasibility of isolating such intact mucous granules from columnar epithelial cells.
These studies have focused on mucus secretion at an organ or tissue level. Spectra were collected from samples at room temperature and corrections were made for beam-induced mass loss. There is a sudden release of calcium from the mucous secretory granules which occurs immediately preceding the release of granule contents, a step which is often associated with fusion of the membrane of the secretory granule with the apical plasma membrane. The Novartis Foundation, originally known as the Ciba Foundation, is well known to scientists and clinicians around the world. Also, the proximal jejunum was more responsive to the carbachol stimulus mucus secretion rate of 5. The E-mail message field is required.
In vitro mucoadhesion studies with Polycarbophil disks were performed in the mucosal tissues of the stomach, jejunum, cecum and proximal colon of the rat with and without cholinergic carbachol stimulus. For immunofluorescence studies, dog gallbladder epithelial cells were grown on glass coverslips. However, occasionally cells which had their intracellular mucous granules released extracellularly could be seen with the contents expanded to acquire the form of a spherical mass. These were post-fixed in osmic acid and dehydrated in graded ethanol. The present experiments were designed to assert the presence of an intragranular shielding cation and its role in secretion. Briefly, 5 ml of bile was saturated with ammonium sulfate. Carbachol treatment did not significantly change the mucoadhesion of Polycarbophil disks.
The huge molecular weight of mucins 2—10 × 10 6 would mean hours before any passive diffusion would reach equilibrium. The culmination of these events is generally considered to be fusion of the cytoplasmic mucin granule membrane with the plasma membrane, the process of exocytosis, with complete incorporation of the granule membrane into the apical plasma membrane. Spherules of secreted mucus larger than intracellular granules were noted on scanning electron microscopy. We had proposed that mucins must be condensed in the secretory granule and expand by hydration during or after exocytosis Verdugo, 1984; Tam and Verdugo, 1981. These spherules ranged from 0. Biochim Biophys Acta 825 : 365- 374.
The evidence for these putative oesophageal defence mechanisms is discussed. That the mucous granule, in the form of a tightly packed and condensed network of polyions, once released of its cationic shielding, will rapidly expand according to a Donnan equilibrium process ; ; and can be immediately hydrated with the optimum amount of extracellular fluid is also predicted by this hypothesis. Glass who took the photographs. We studied mucous granule exocytosis in gallbladder epithelium, a model system for mucus secretion by columnar epithelial cells. Biophys J 43: 355- 369.
Cholecystectomies were performed on 35 mice and gallbladder mucus was collected by scraping away the native mucus gel with a glass slide. Other detailed fine structures of the mouse gallbladder epithelial cell have been described elsewhere ;. This article reviews the mechanisms involved in protecting the oesophagus against acid-mediated injury, including the role of the lower oesophageal sphincter, secondary oesophageal peristalsis and swallowed saliva. This hypothesis also describes a common intracellular pathway in the control of mucus secretion, whether this is initiated by chemical mediators , by adrenergic, peptidergic , or cholinergic ; mechanisms. Four weeks thereafter rabbits were given a booster injection 0.
Local actions may play a role in accelerating healing of ulcer-damaged mucosa, but this does not explain the protective actions of sucralfate on normal mucosa. That is, the rate of swelling was dependent on the pH and ionic concentration in the extracellular gel medium. Functional data for chloride channel involvement in mucous granule exocytosis is beyond the scope of this report. Antibody activity was confirmed using the tube precipitin test, double diffusion in agarose, and binding to immobilized mucus on cellulose nitrate membranes. Regardless of the trigger signal, any model of the molecular mechanism of mucus secretion must account for the observation that within the cell, the mucous granule is extremely tightly packed and condensed, usually contains an excess negative charge, and is relatively underhydrated.
However, the importance of bicarbonate secretion to mucosal integrity within the proximal gut remains uncertain. The Novartis Foundation, originally known as the Ciba Foundation, is well known to scientists and clinicians around the world. Thus, the proposed spring-loaded release system based on the unshielding of a condensed polyion may serve as a general model for explaining the molecular mechanism of product release in secretion. No apparent or absolute molecular weight cut-off for macromolecular transfer was exhibited. At midcycle there was a tendency for the mucus to condense into globules which were linked together like strings of varying sized beads. Sucralfate has also been shown to increase the hydrophobicity of mucus gel.