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Macromolecular and lipid constituents of bronchial epithelial mucus.

The physical and chemical properties of bronchial epithelial mucus depend on its special mix of macromolecules and lipid constituents: these are different in the normal airway under baseline conditions from one stimulated acutely, and show major modification in disease. Since the last conference, density gradient ultracentrifugation has been extended to the study of normal bronchial mucus in addition to that of sputum from patients with chronic bronchitis, cystic fibrosis and asthma, and has revealed striking differences between the chemical profiles of normal and hypersecretory mucus. Normal mucus represented individual bronchial aspirates, obtained at fiberoptic bronchoscopy from healthy human volunteers (non-smokers), aspirates from normal dogs (before SO2 exposure in a canine model of SO2 induced bronchitis) and secretions released in vitro by human bronchial and canine tracheal explants. Mucus 'in transition' included aspirates from otherwise healthy smokers and from dogs early in irritation. Hypersecretory mucus included, besides those mentioned above, aspirates from dogs that had developed bronchitis and the excessive mucus produced by some patients with acute quadriplegia. Lipids. In normal mucus, human (unpooled) and canine, neutral lipids are the predominant species, with lesser amount of phospholipids: no glycolipids are detected. The first qualitative change on irritation, even before macromolecular yield increases, is appearance of glycolipids. In hypersecretory mucus, human (including quadriplegics) or canine, glycolipids are detected in appreciable amounts and often are the predominant species: they include complex forms such as sialic acid containing gangliosides. Organ and cell culture studies establish that these lipids are produced by airway epithelial cells. These lipids are important to gel formation. Glycoconjugates. A major recent advance is the recognition that normal mucus does not contain typical epithelial glycoprotein. Its glycoconjugate is of higher density with sugars typical of both glycoprotein (GP) and proteoglycan (PG) and with an amino acid profile more akin to PG (glycine greater than serine greater than threonine). In transition to hypersecretion, a 'mixed molecule' changes its sugar mix to produce a density typical of GP. In hypersecretion, the epithelial GP develops a typical buoyant density and amino acid profile (threonine greater than serine greater than glycine). Organ culture of bronchial explants, and more recently cell culture, establish that the PGs are major products of airway secretory cells. The normal airway is capable of producing glycoprotein on cholinergic stimulation. The range of glycoconjugates present in the secretion support the wide range of granule and cell features identified in vivo. Monoclonal antibody raised to a pure preparation of bronchial epithelial glycoprotein reacts with mucous cells in the surface epithelium and also in the submucosal gland in both human and canine airways.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Structure and macromolecular properties of cervical mucus glycoproteins.

The endocervical canal is filled with a mucus gel, the properties of which vary during the ovulatory cycle. At mid-cycle the amount of mucus increases, mainly owing to an oestrogen-induced increased hydration of the gel, mucus becomes less visco-elastic and the penetration of the spermatozoa is facilitated. In contrast, under the influence of progesterone during the luteal phase, mucus turns into a less hydrated, highly visco-elastic structure which acts as a barrier to sperm. The mucus gel is formed by very large and structurally complex glycoproteins perfected by evolution to tease and disunite the scientists engaged in unravelling their secrets. The macromolecules are referred to as the mucus glycoproteins or the mucins. Hydrodynamic studies show that cervical mucus glycoproteins (Mr 10-15 x 10(6] behave as random coils, which occupy large spheroidal domains in dilute solution. The predicted 'linear' structure is supported by evidence obtained with electron microscopy. By this technique, the macromolecules are visualized as 'threads' with a skewed and polydisperse distribution of contour lengths (number-average length, 1.5 microns; range 0.5-5 microns). The macromolecules may be cleaved into subunits (Mr 2-3 x 10(6] by reduction of disulphine bonds and these fragments can be divided into large glycopeptides (T-domains; Mr 300,000-400,000) by trypsin. Most of the carbohydrate, which accounts for approximately 80% by weight of the macromolecule and occurs as a heterogeneous population of oligosaccharides, is enriched within the T-domains. The high-Mr glycopeptides thus correspond to long (of the order 100 nm) stretches of protein covered with 100-300 oligosaccharides which protect the core from proteolysis. These regions of the macromolecule are referred to as oligosaccharide 'clusters' and subunits of cervical mucins contain, on average, 3-5 of these 'clusters'. Each 'cluster' is flanked by stretches of protein which are less substituted with carbohydrate and, consequently, more sensitive to proteolysis. There is evidence that these parts of the core, referred to as the 'naked' regins, are folded and stabilized by disulphide bonds. Cervical mucus glycoproteins may thus be viewed as a linear array of oligosaccharide-rich 'clusters' alternating with structures reminiscent of a globular protein. Little is known about how the mucus glycoproteins interact to form the gel. The classical 'Odeblad concept' postulates that the mucins form bundles ('micelles') which are then interconnected in a hormone-dependent way. In contrast, light-scattering studies suggest that cervical mucus is an entangled net-work of long and flexible macromolecules.(ABSTRACT TRUNCATED AT 400 WORDS)

Carbohydrate Sequence↗

Prolactin in human cervical mucus.

The pattern of change in the levels of prolactin (PRL) in cervical mucus was studied in 19 normal ovulatory women. The concentration of PRL in cervical mucus was generally higher than that in plasma except at midcycle, when a reverse relationship was observed. The concentration of PRL in mucus obtained at midcycle was lower than mucus obtained during follicular phase or luteal phase. There were no significant differences in the total PRL content among preovulatory, midcycle and postovulatory cervical mucus samples. The amount of cervical mucus markedly increased during the periovulatory period (two days from the peak of plasma luteinizing hormone). The cervical mucus PRL level undergoes cyclic changes during the normal menstrual cycle, and the decrease in PRL concentration in mucus at midcycle is most likely a result of the dilutional effect of increased mucus volume. The physiological implication of the presence of PRL in human cervical mucus is also discussed.

Cervix Mucus↗

The mucus barrier. Its role in gastroduodenal mucosal protection.

A layer of water-insoluble mucus gel has been shown to form a continuous cover over the gastroduodenal mucosal surfaces, of median thickness of 180 micron in stomach in humans. This adherent mucus is the first line in mucosal defence against the natural aggressors, acid and pepsin, in the lumen. Mucus gel provides a stable unstirred layer that supports surface neutralisation of acid by mucosal bicarbonate. Mucus gel is a diffusion barrier to pepsin in the lumen, preventing proteolysis of the underlying epithelial cells. There is, however, a dynamic balance between digestion by pepsin of the mucus layer at its luminal aspect and secretion of new mucus by the epithelium. There is evidence that, in peptic ulcer disease, the rate of peptic degradation of the mucus barrier is increased. Exogenous damaging agents such as ethanol and aspirin permeate the gel matrix of the mucus barrier, rapidly damaging the underlying epithelium. The subsequent reepithelialisation process is protected by a gelatinous coat over ten times thicker than the original adherent mucus layer. This gelatinous coat is primarily a fibrin-based gel with necrotic cells and mucus.

Animals↗

Entry of [3H]water and [1,2-14C]polyethylene glycol 4000 into normal and cystic fibrosis salivary mucus.

This investigation was performed to compare the entry of [3H]water and [14C]PEG into samples of salivary mucus from patients with CF and normal subjects. A solution containing both radioisotopes was added to samples of salivary mucus and mixed, and entry of each into mucus was determined by their dilution in the supernatant at 1, 2, 4, and 24 hr. [3H]water rapidly entered and equilibrated with the water content of both normal and CF mucus. [14C]PEG entered mucus more slowly than [3H]water and by 24 hr had entered at a ratio of only 0.794 +/- 0.108 and 0.766 +/- 0.039 of the water space accessible to [3H]water in normal and CF mucus, respectively. The mechanisms responsible for the partial exclusion of the large polyethylene glycol molecule were not explored but may reflect steric restriction of access to a portion of mucus water. Thus water entry and solute exclusion, both determinants of permeability, were unaltered in CF mucus, which fact provides evidence against the presence of a generalized defect of mucus permeability in this disease. The techniques developed for this study may be adaptable to the study of the permeability properties of mucus from other sources and other gels.

Adolescent↗

Luteinizing hormone in cervical mucus.

The presence of material like luteinizing hormone (LH) in cervical mucus has not been previously reported. In this study, we show that in human cervical mucus there is LH-like material detectable by radioimmunoassay (RIA) and by bioassay. The content of LH in the cervical mucus of five donors was measured by RIA in samples of mucus obtained daily throughout the menstrual cycle. The concentration of LH in mucus obtained during ovulation was lower than in mucus obtained during the early follicular phase or mucus obtained during the luteal phase. This material exhibits LH-like biologic activity because increasing volumes of cervical mucus added to isolated mice Leydig cells stimulates testosterone secretion by these cells, in a parallel dose-related fashion, to increasing quantities of human chorionic gonadotropin (hCG). No immunologic cross-reactivity of the cervical mucus was observed with an antiserum specific for the beta-subunit of hCG. Taken together, the results of the present study suggest the presence of an LH-like substance within the cervical mucus that exhibits both the immunologic and biologic properties of LH.

Animals↗

The frog palate mucosa as a model for studying bacterial adhesion to mucus-coated respiratory epithelium.

Most of the methods proposed to quantify bacterial adherence to respiratory mucosa differ mainly from in vivo conditions in the absence of the mucus blanket and in the exposure of the sub-mucosal connective tissue (SMCT) to the micro-organisms. We propose the frog palate as a model to study bacterial adhesion to the respiratory mucosa, with a system which allows the mucus to be preserved and the bacterial adhesion to be quantified in a standardized mucosal area, where mucociliary transport is still active. In order to evaluate the role of respiratory mucus in bacteria-mucosa interaction, we compared the adhesion of radiolabelled pneumococci to 12 mucus-coated and 10 non-mucus-coated frog palate mucosae. The presence or absence of mucus was controlled by scanning electron microscopy (SEM). After a 10 min incubation period, the bacterial adhesion to mucus-coated palate mucosa was five times greater (P less than 0.01) than that to uncoated mucosa. By SEM, bacteria were never seen attached to ciliated cells but could be detected on small areas where mucus was not totally eliminated. Even after a 120 min contact of bacteria to uncoated mucosa, bacterial adhesion remained only half that to mucus-coated epithelium. In order to ascertain whether the exposure of the SMCT represented a means of attraction to bacteria, we incubated the frog palate mucosa face-down with radiolabelled Pseudomonas aeruginosa. As much as 44 per cent of added bacteria adhered to exposed SMCT and, by SEM, numerous micro-organisms were seen attached to connective tissue. In contrast, only a few bacteria were observed adhering to the mucosa, mainly to granules of mucus.

Animals↗

Videolaryngostroboscopic observation of mucus layer during vocal cord vibration in patients with vocal nodules before and after surgery.

OBJECTIVE: Under normal conditions, the vocal fold mucus layer is too thin to permit observation using videolaryngostroboscopy (VLS) during phonation. However, vocal nodules (VNs) typically cause congealed and sticky mucus to appear on the vocal fold. Reports in the literature regarding this phenomenon are limited. The aim of this study was to review VLS recordings of VN patients, analyzing changes that occurred in the mucus layer that covers the vocal fold during vibration following VN surgery. MATERIAL AND METHODS: Using VLS, we studied the occurrence of, and changes in, vocal fold mucus layers in 160 VN patients before and after surgery. RESULTS: Eighty-eight patients (55%) were found to have a mucus layer during preoperative examinations. Of these mucus layers, 21 (13%) were located on the anterior commissure or anterior third of the vocal fold (A), 58 (36.3%) on the junction of the anterior and middle thirds (M), 1 (0.6%) on the posterior third (P), 5 (3.1%) on both A and M and 3 (1.9%) on both M and P. Fifty-six (35%) cases were found to have a mucus layer during postoperative examinations. Of these, 44 (27.5%) were located on A, 8 (5%) on M, 1 (0.6%) on P and 3 (1.9%) on both A and M. These results indicate that changes in the mechanical force on the vocal fold, alteration of the laryngeal secretory gland and improper aerodynamic airflow result in increased mucus viscosity and aggregation in VN patients and that the combination of these factors further increases the severity of dysphonia. CONCLUSIONS: Surgery to remove vocal nodes may be an effective method to eliminate both vocal bumps and aggregated mucus. Based on the present results, it is recommended that future research should compare surgery to remove VN against other mucus layer reduction methods in order to determine which is the most effective.

Adult↗

Ammonia produced by Campylobacter pylori neutralizes H+ moving through gastric mucus.

We aimed to show that Campylobacter pylori infection increases the concentration of ammonia in the gastric mucus and alters the movement of H+ through the mucus. Mucus from uninfected and C. pylori-infected stomachs was collected at postmortem. Ammonia was measured enzymatically. The ammonia concentration in C. pylori-infected mucus was fourfold greater than in uninfected mucus. H+ movement experiments were carried out using an in vitro chamber, in which a layer of mucus separated a 0.1 M HCl solution from distilled H2O. The change in pH of the distilled H2O was measured over 30 min. A drop in pH was measured for uninfected mucus. A slight rise in pH was measured for C. pylori-infected mucus. We conclude that C. pylori infection is associated with reduced H+ movement through mucus and that this may be due to increased ammonia concentration within mucus.

Ammonia↗

A novel method for the visualization of the in situ mucus layer in rat and man.

1. The observed thickness of the gastric mucus barrier varies widely, even appearing discontinuous, depending on the methods used. Here we describe the development and application of a modified periodic acid Schiff/Alcian Blue staining technique for use on cryostat sections of gastric mucosa. This technique for the first time enables the preservation and visualization of the full thickness of the adherent gastric mucus layer and the underlying mucosa. 2. In designing this novel method we have selected those procedures which would result in the least alteration to the mucus layer. The methods used were snap freezing, cryostat sectioning of the whole stomach followed by brief ethanol pretreatment (10 min in 100% ethanol), a prolonged staining with periodic acid Schiff/Alcian Blue (15 min and 2.5 h respectively), a gentle post-fixation (45 min paraformaldehyde vapour at 37 degreesC) and the use of a water-soluble mountant. 3. A continuous, adherent mucus layer was observed over the surface of the rat gastric mucosa (periodic acid Schiff/Alcian Blue stained) and human gastric antral biopsies (periodic acid Schiff stained). In the rat the mean (S.D.) mucus thickness measurements along the antrum to oesophageal axis (which was divided histologically into four regions, A to D) were: A, 166 (47) micrometer; B, 179 (48) micrometer; C, 184 (50) micrometer; D (the non-glandular stratified epithelium at the top of the stomach), Absent. In human gastric antral biopsies the mean (S.D.) mucus thickness was 144 (52) micrometer. 4. This new technique has enabled the visualization and precise measurement of thickness of the gastric mucus layer in rat and man. The adherent gastric mucus layer was observed to be continuous in the rat glandular stomach and human antrum. In validation experiments in rat the mean mucus thickness measurements were found to be twice those measured by conventional histological techniques, in which the mucus layer appeared discontinuous and patchy. However, they were within the range of thickness values seen in unfixed tissues and in the rat in vivo preparation.

Aged↗

Timing of onset of contraceptive effectiveness in Depo-Provera users: Part I. Changes in cervical mucus.

OBJECTIVE: To evaluate the changes in cervical mucus within the first hours or days after depot medroxyprogesterone acetate (MPA) injection so as to estimate the time at which cervical mucus becomes hostile enough to prevent pregnancy. DESIGN: Multicenter, clinical descriptive study. SETTING: Family planning clinic. PATIENT(S): Thirty women who were between days 8 and 13 of their menstrual cycle and who had requested Depo-Provera were enrolled in the study. INTERVENTION(S): Cervical mucus and blood samples were obtained; transvaginal ultrasonography was performed. MAIN OUTCOME MEASURE(S): Cervical mucus scores, sperm penetration distances, ovarian follicular size, and serum levels of progesterone and estradiol. RESULT(S): From 6 to 24 hours after injection, there was a sharp decline in the cervical mucus score for most of the subjects. All subjects exhibited poor mucus on day 3 after injection, and by day 7, all subjects had zero scores, with the exception of two outliers on each day. Sperm penetration, as measured by the vanguard sperm distance, was already poor (< 1 cm) in 7 of the 30 subjects at the time of injection and was reduced progressively up to 24 hours after injection, when only four subjects had a sperm penetration of > 1 cm. A rapid decline in the estimated number of sperm was observed at 12 hours and more so at 24 hours in the majority of subjects. CONCLUSION(S): The data presented in this report confirmed that depot MPA causes profound changes in cervical mucus after injection. Although very little change was seen at 6 hours, alterations were observed subsequently, with 90% of the subjects showing a poor cervical mucus score 24 hours after administration of the progestin. No reliable clinical marker is available to identify in which women depot MPA might exert its effect on cervical mucus within 3 days. Thus, we believe that at present, women should be informed of this uncertainty and should use a backup method of contraception for 7 days when the first injection of depot MPA is provided after the seventh day of the menstrual cycle.

Adult↗

Factors influencing the success of sperm-cervical mucus interaction in patients exhibiting unexplained infertility.

The factors regulating the success of sperm-cervical mucus interaction in 46 patients exhibiting unexplained infertility were analyzed. Within this group of patients, considerable variation in the degree of mucus penetration, which appeared to be related to the properties exhibited by the spermatozoa rather than the quality of the mucus itself, was observed. The ability of the spermatozoa to fuse with zona-free hamster oocytes reflected their capacity for mucus penetration, regardless of whether human or bovine cervical mucus was used as the target. Multiple regression analysis also indicated the importance of the movement characteristics exhibited by the spermatozoa, which alone could account for up to 85% of the variability in mucus penetration. The concentration of motile spermatozoa and their linear velocity of progression influenced the number of spermatozoa penetrating the mucus in unit time, presumably through an effect on the frequency of collisions at the cervical mucus interface. Whether these collisions resulted in mucus penetration depended upon the movement characteristics of the spermatozoa and was positively associated with a "rolling" mode of progression and the amplitude of lateral sperm head displacement.

Animals↗

The influence of mucus on copper speciation in the gill microenvironment of carp (Cyprinus carpio).

pH and mucus (as total organic carbon) in the gill microenvironment of carp, Cyprinus carpio, exposed to various concentrations of total copper were measured in an exposure experiment using Playle's apparatus. The activities of free copper ions in both inspired and expired waters were determined using a copper ion selective electrode. A trial-and-error procedure of coupling species distribution calculations (MINEQA2) with single-site complexation modeling (mucus-copper) was proposed for computation of both copper speciation and complexation capacity of gill mucus for copper in an interactive loop. The method was demonstrated to be valid in calculating the metal speciation in this study. It was found that pH and alkalinity in the gill microenvironment were slightly higher than in the surrounding water of pH 6.7. The rates of excretion of CO(2), HCO(-)(3), and mucus at the gills increased, either linearly or nonlinearly with increases in the total copper concentration in the surrounding water. The conditional complexation stability constant of the mucus was calculated as log k=5.32, while the complexation stability equivalent concentration of the mucus was derived as 0.95 mmolCu/mgC. As a consequence of changes in pH and alkalinity, in conjunction with occurrence of mucus, copper speciation in the gill microenvironment is significantly different from that in the surrounding water, with 3-20% of the copper complexed by the gill mucus. The sequence of species domination also shifted from CuCO(0)(3), Cu(2+), CuHCO(+)(3), and Cu(OH)(0)(2) in the surrounding water to CuCO(0)(3), Cu(2+), Cu(OH)(0)(2), CuHCO(+)(3), and mucus-Cu in the gill microenvironment.

Animals↗

Changes in the electrophoretic profiles of gill mucus proteases of the eastern oyster Crassostrea virginica in response to infection by the turbellarian Urastoma cyprinae.

Urastoma cyprinae occurs on the gills of various bivalves species, including the eastern oyster Crassostrea virginica. While the worm is known to cause severe gill disruption in mussels, no evidence of this nature has been described for oysters. Nonetheless, high levels of U. cyprinae have been reported in oysters, which may, in turn, reduce the oyster's overall condition. U. cyprinae is strongly attracted to oyster gill mucus, which is suggested to play an active role in the worm's feeding activities. Furthermore, host mucus contains many active components, including proteases, which have been suggested to play a defensive role against invading organisms. It follows, therefore, that some of the interactions between U. cyprinae and oysters take place in host gill mucus. Studies were undertaken to determine whether the presence of U. cyprinae altered the electrophoretic profiles of oyster gill mucus, using proteases as indicators. Findings reveal that oyster gill mucus contains three proteases, a putative acid protease at 96 kDa, a zinc metalloprotease at 64 kDa, and a serine protease at 33 kDa. Results based on experiments using mucus preparations extracted from infected and noninfected oysters, along with those using lyophilized mucus incubated with live U. cyprinae, confirm that the presence of U. cyprinae alters the protease composition of gill mucus. The present data demonstrate that both U. cyprinae and host gill mucus actively secrete proteases. While the precise roles of these enzymes still need to be defined, one of their functions may be associated with digestion-related activities induced by the worm.

Animals↗

A functional model for extracellular gastric mucus in the rat.

There is no morphologically detectable, continuous layer of extracellular mucus over the undamaged gastric mucosa of the rat. Instead, the mucosa is only partially covered by an interconnected network of mucous strands and sheets. This mucus is strongly acidic (sulphated) and is released by epithelial cells which line the isthmic and lower foveolar regions of the gastric glands of the fundus. A thick layer of gelatinous mucus is, however, released within 5 min after topical application of ulcerogenic agents. This mucus is released as a result of exfoliation and disintegration of interfoveolar surface epithelial cells. The released mucous glycoprotein is neutral or weakly acidic and is readily distinguished from the fibrous mucus produced by the epithelial cells which line the upper regions of the gastric glands. The preexisting network of acidic, fibrous mucus is retained at the luminal surface of the mucous cap which is produced over sites of damage. The layer of fibrous mucus is reinforced during the development of mucosal damage by accelerated release of mucous strands from the gastric glands. We propose that the fibrous mucus acts as an external, restraining layer to maintain the locally released, gelatinous mucus over sites of damage during a period in which epithelial continuity is restored by emigration of cells from the gastric glands.

Animals↗

Airway mucus membrane: effects of beta-adrenergic and anticholinergic stimulation.

Mucus hypersecretion and non-continuous clearance of tracheobronchial mucus contribute to airflow obstruction in several pulmonary disease entities. Bronchospasm, which is frequently associated with bronchial asthma, can present simultaneously with mucus transport abnormalities. Therapy designed to dilate airways may produce secondary effects, which are deleterious to effective transport of lung mucus. Sympathomimetic agents, such as beta-adrenergic agonists, reduce the tone of bronchial smooth muscle and enhance the flow of mucus within lung airways. Parasympatholytic agents also improve airflow in the lungs, but their effects at the mucus membrane of the airways may not be beneficial. Atropine, an anticholinergic agent, apparently has dose-dependent effects on human mucociliary function and, administered orally, can reduce large airway mucus transport. However, newer anticholinergic agents, such as ipratropium bromide, are effective bronchodilators and do not exhibit unfavorable effects on lung mucus transport in either subjects with normal mucus secretion or those with hypersecretory disease entities, such as bronchitis. In mildly symptomatic asthmatic patients, aerosolized ipratropium decreased airway obstruction without consistent positive or negative influence on lung mucociliary function.

Adrenergic beta-Agonists↗

Mucus glycoprotein gels. Role of glycoprotein polymeric structure and carbohydrate side-chains in gel-formation.

The structure of mucus glycoprotein gels from the pig gastrointestinal tract was investigated by mechanical spectroscopy. Gastric, duodenal, and colonic mucus had the same mechanical profile, characteristic of a viscoelastic gel. The gel structure collapsed on destruction of the polymeric structure of the component glycoprotein by reduction with 0.2M mercaptoethanol or after proteolysis with papain. The progressive weakening of mechanical properties and the decrease in polymeric glycoprotein content were measured as functions of time of reduction. A linear correlation was obtained between the gel quality [defined by tan delta, the ratio of the loss modulus (G'') to the storage modulus (G')] and the proportion of polymeric to subunit glycoprotein in the mucus. Purified mucus glycoprotein, at the same concentration as that in native mucus, resulted in a gel with mechanical properties no different from those of the respective native secretion, demonstrating that the glycoprotein alone could reproduce the gel-forming properties of mucus. After proteolytic digestion, all native secretions and reconstituted mucus showed an absence of Newtonian behaviour in the frequency dependence of dynamic viscosity at low frequencies. This provided evidence that the noncovalent interactions, characteristic of the native gel matrix, were still present after proteolytic digestion when the nonglycosylated protein core accessible to proteinases had been removed. These results were interpreted to show (a) a common mechanism for gel-formation in gastric, duodenal, and colonic mucus; (b) that the polymeric structure of mucus glycoproteins confers the three-dimensional structure necessary for formation of the gel network; and (c) that noncovalent interactions which arise between the glycoprotein molecules by relatively stable interdigitation of the carbohydrate side-chains are involved in formation of the gel network.

Animals↗

Mucus and alkali secretion in the rat duodenum: effects of indomethacin, N omega-nitro-L-arginine, and luminal acid.

BACKGROUND & AIMS: Duodenal mucus and bicarbonate secretion appear to play an essential role in the protection of the duodenum. The aim of this study was to examine duodenal bicarbonate and mucus secretion and the effects of cyclooxygenase inhibition, nitric oxide synthase inhibition, and luminal acid. METHODS: Duodenal mucus gel thickness was measured using microelectrodes during intravital microscopy in anesthetized rats. Bicarbonate secretion was measured using back-titration. RESULTS: A continuous layer of mucus with a mean thickness of 284 +/- 11 microns (n = 35) and a mean alkaline secretion of 0.18 +/- 0.01 mumol.cm-2.min-1 were found in untreated animals. Indomethacin decreased both mucus and bicarbonate secretion by about 35%. NO synthase inhibition with N omega-nitro-L-arginine reduced mucus secretion by about 21% but increased bicarbonate secretion by 39%. Exposure of the mucosal surface to 10 mmol/L HCI increased mucus secretion by 44% and bicarbonate secretion by 22%. CONCLUSIONS: The duodenal mucus layer is continuous. It can be easily removed, and new secretion can be followed. Duodenal mucus secretion is strongly stimulated by luminal acid and endogenous prostanoids and less markedly by NO, whereas bicarbonate secretion is stimulated by acid and endogenous prostanoids and inhibited by endogenous NO.

Acids↗