Mucus Output Research Articles

The effects of peptide histidine isoleucine and neuropeptide Y on mucus volume output from the ferret trachea.

1. The effects of peptide histidine isoleucine (PHI) and neuropeptide Y (NPY) were examined on the mucus volume output produced by methacholine and phenylephrine in the ferret whole trachea in vitro. 2. Sustained application of methacholine (5 microM) or phenylephrine (20 microM) produced a maintained volume output of mucus from the trachea. Both these agonists also increased the output of lysozyme (a marker for serous cell secretion). 3. PHI inhibited the maintained mucus volume output produced by methacholine but had no effect on that due to phenylephrine. The output of lysozyme produced by methacholine or phenylephrine was not significantly changed by PHI. 4. NPY enhanced the volume output of mucus produced by methacholine or phenylephrine; however, the rate of output of lysozyme in mucus produced by both agonists was reduced by NPY. 5. We suggest that PHI has no effect on serous cell secretion but inhibits secretion from another source, possibly mucous cells. NPY inhibits serous cell secretion but has a stronger stimulant action on secretion from another source, again possibly mucous cells. 6. PHI and NPY may be important physiological modulators of mucus volume output in the ferret trachea.

Action of a novel drug (Zy 16039) on mucus secretion in the ferret isolated trachea in vitro.

1. The effect of 4-H-2-carboxamido-4-phenyl-thieno-[3,2c]-[1]-benzopyran (Zy 16039) was examined on the smooth muscle contraction, mucus secretion and albumin transudation in the ferret whole trachea in vitro. 2. Zy 16039 (0.1-20 microM) produced a concentration-dependent relaxation of the ferret trachea contracted by methacholine (1 microM) and phenylephrine (10 microM). The relaxations were about 20% of the full contractions. 3. Zy 16039 has no effect on the resting (zero) output of mucus in the ferret trachea. Methacholine-induced mucus secretion was significantly inhibited by Zy 16039, whereas phenylephrine-induced secretion was significantly increased. 4. Methacholine-induced secretion of lysozyme, a marker of serous cell secretion, was inhibited by Zy 16039 both with regard to output and concentration of lysozyme. In contrast, Zy 16039 significantly increased the output of lysozyme due to phenylephrine, with no effect on concentration. 5. Zy 16039 had no significant effect on the rate of output of fluorescent albumin through the tracheal wall. However the concentration of albumin in the mucus samples was changed because of the effect of Zy 16039 on mucus secretion induced by methacholine and phenylephrine. 6. We conclude that Zy 16039 relaxes airway smooth muscle, and either promotes or inhibits mucus secretion depending on its source. It has qualitatively similar actions to vasoactive intestinal peptide.

Comparison of mucus flow rate, radiolabelled glycoprotein output and smooth muscle contraction in the ferret trachea in vitro.

1. The concentration-response curves for rate of mucus output, labelled-glycoprotein output and smooth muscle contraction in response to methacholine, phenylephrine and salbutamol were determined in the ferret trachea in vitro. 2. The potencies of methacholine and phenylephrine are both in order: smooth muscle contraction, glycoprotein output, rate of mucus output. 3. At lower concentrations methacholine is more potent than is phenylephrine on smooth muscle contraction, glycoprotein output and rate of mucus output. 4. Concentration-response curves for salbutamol show very little change in rate of mucus output but a large increase in glycoprotein output. 5. It is concluded that the glycoprotein output induced by salbutamol may come from a source different from those induced by methacholine and phenylephrine.

In situ release of mucus and DOC-lipid from the corals Acropora variabilis and Stylophora pistillata in different light regimes

Rates of mucus and DOC-lipid release were determined for colonies of Acropora variabilis and Stylophora pistillata at 5 m depth and for a colony of A. variabilis at 23 m depth. In addition, colonies at 5 m were shaded to simulate ambient irradiance at 6 m, 10 m and 16 m depth to evaluate the effect of light on the rates of release. A. variabilis released more mucus and DOC-lipid at 5 m than at 23 m depth. For both corals, the night rates were about 30% those of the day. A reduction in total integrated irradiance decreased mucus output from the corals. Similarly, DOC-lipid release showed a diurnal pattern and diminished with reduction in daily irradiance. For both coral species, DOC-lipid release rates were greater in the afternoon than in the morning. The night rates were less than 55% those of the day. The DOC-lipid comprised wax esters and a phospholipid fraction. The diurnal variation was due to changes in yield of wax esters which contributed >90% of the carbon released as DOC-lipid. In situ release of mucus and DOC-lipid was infuenced by light effects on phototrophic carbon metabolism. A daily budget for carbon released as mucus and DOC-lipid was estimated for each coral species at 5 m depth.

Effects of Trimoprostil, a prostaglandin E2 analogue, on human gastric acid secretion and soluble mucin output

We have studied the effects of Trimoprostil, a prostaglandin E2 analogue, on gastric acid and soluble mucus output using human subjects. This compound caused anti-secretory effects on both basal as well as histamine-stimulated gastric acid secretion in a dose-dependent manner. There was a simultaneous increase in total mucus output. When the secreted mucus was fractionated by Sepharose CL-2B gel chromatography, most of the basal gastric mucin was shown to be in the polymeric form (mol wt 2 X 10(6)), whereas after histamine stimulation the mucin was mostly in the subunit form (mol wt 0.5 X 10(6)). The gastric mucin, after stimulation using low doses of prostaglandin, was mainly in the polymeric form; but after higher doses, the subunit form predominated. These observations are important in the understanding of physiological and pharmacological control of gastric mucus output with regard to its chemical composition and molecular heterogeneity, and provide further insight into the rational clinical use of the prostaglandins for gastroduodenal diseases.

Influence of vasoactive intestinal peptide, secretin, and Ala4, Val5-secretin on the net movements of electrolytes, fluid, and mucus in the rat colon in vivo.

The effect of vasoactive intestinal peptide (VIP), secretin, and VIP-secretin (Ala4, Val5-secretin) on the net movements of sodium, potassium, fluid, and mucus was investigated in the rat colon perfused in vivo. Peptides (1-100 micrograms/kg.h) were infused intra-arterially. VIP influenced electrolyte and fluid movements at a threshold dose 10- to 100-fold lower than secretin, whereas the secretory efficacy was not significantly different. Replacing the NH2-terminal hexapeptide of secretin by that of VIP did not markedly alter the effect of secretin. Mucus output was stimulated weakly by all three peptides. The results indicate that the larger colonic secretory activity of VIP as compared to secretin is not primarily due to the difference in their NH2-terminal sequence but probably requires the intact molecule.

Gastric protection by sucralfate: Role of mucus and prostaglandins

Sucralfate promotes the healing of peptic ulcers and, in large doses, increases gastric mucosal prostaglandins. The present study was designed to further elucidate the protective effect of sucralfate and to evaluate the role of prostaglandins in this action. Eight chair-adapted rhesus monkeys received a subcutaneous injection of either 150 mg/kg of aspirin or vehicle in combination with either a therapeutic oral dose of sucralfate (50 mg/kg · day) or water. Gastric soluble mucus concentration was determined in samples of gastric juice by Alcian blue dye binding of acidic glycoproteins, and mucus output was determined using a technetium 99m-diethylenetriaminepentaacetic acid dilution technique. Monkeys underwent endoscopy to assess gastric mucosal damage, which was ranked blindly on a scale of 0–5, and to obtain biopsy specimens for determination of mucosal prostaglandin E2, prostaglandi F2α, and 6-keto-prostaglandin F1α. Aspirin did not alter soluble mucus but did significantly increase gastric mucosal damage and suppress tissue levels of all prostaglandins. Sucralfate significantly increased the output of soluble mucus, even after aspirin treatment, and protected against aspirin-induced damage, although it did not modify aspirin-induced suppression of prostaglandins. These results suggest that the gastric protection afforded by sucralfate is related to a prostaglandin-independent increase in mucus production.

Gastric protection by sucralfate

Abstract Sucralfate promotes the healing of peptic ulcers and, in large doses, increases gastric mucosal prostaglandins. The present study was designed to further elucidate the protective effect of sucralfate and to evaluate the role of prostaglandins in this action. Eight chair-adapted rhesus monkeys received a subcutaneous injection of either 150 mg/kg of aspirin or vehicle in combination with either a therapeutic oral dose of sucralfate (50 mg/kg · day) or water. Gastric soluble mucus concentration was determined in samples of gastric juice by Alcian blue dye binding of acidic glycoproteins, and mucus output was determined using a technetium 99m-diethylenetriaminepentaacetic acid dilution technique. Monkeys underwent endoscopy to assess gastric mucosal damage, which was ranked blindly on a scale of 0–5, and to obtain biopsy specimens for determination of mucosal prostaglandin E 2 , prostaglandi F 2α , and 6-keto-prostaglandin F 1α . Aspirin did not alter soluble mucus but did significantly increase gastric mucosal damage and suppress tissue levels of all prostaglandins. Sucralfate significantly increased the output of soluble mucus, even after aspirin treatment, and protected against aspirin-induced damage, although it did not modify aspirin-induced suppression of prostaglandins. These results suggest that the gastric protection afforded by sucralfate is related to a prostaglandin-independent increase in mucus production.

Acid, pepsin, and mucus secretion in patients with gastric and duodenal ulcer before and after colloidal bismuth subcitrate (De-Nol).

Basal and pentagastrin stimulated gastric secretion was measured in seven patients with duodenal, and six with gastric ulcers before and after four weeks' treatment with colloidal bismuth subcitrate (as De-Nol), one tablet four times a day. Each duodenal and all but one of the gastric ulcers healed. After De-Nol there were no significant changes in basal, or pentagastrin stimulated volume, acid output, or primary parietal component. There were marked decreases in basal (duodenal ulcer -25%; gastric ulcer -16%) and pentagastrin stimulated total pepsin outputs, (duodenal ulcer -42%, gastric ulcer -36%). There were insignificant decreases in basal output of mucus, but postpentagastrin stimulated mucus output was significantly inhibited (p less than 0.05) in patients with duodenal (-16%) and with gastric ulcer (-27%). The drop in gastric proteolysis after De-Nol is unlikely to be because of the healing of the ulcers and is more likely to be because of the drug. The ulcer healing efficacy of De-Nol may be related to this decline in the proteolytic action of gastric juice, but is unlikely to be because of a quantitative change in mucus, or in acid secretion.

Misoprostol-induced increases in adherent gastric mucus thickness and luminal mucus output.

Gastroduodenal mucus can be separated into two phases: insoluble mucus gel adherent to the mucosal surface, and luminal mucus, which is removed by washing out the lumen. The adherent mucus gel is part of the mucosal protective barrier to acid and pepsin in the gastric juice. Luminal mucus, which is mobile, probably does not significantly protect against gastric juice, but functions as a lubricant, protecting the adherent mucus layer and underlying mucosa from mechanical damage. Adherent mucus is observed on the mucosal surface as a thin, continuous, gelatinous layer of variable thickness, about 50-450 microns (median, 180 microns) in man and 10-230 microns (median 80 microns) in the rat. Thickness of this adherent mucus layer in the rat stomach is increased significantly (up to threefold) following topical administration of misoprostol in vivo 1 hr before measurement. Simultaneous increases are observed in the content of luminal mucus following misoprostol administration. Seventy percent of maximum response is observed within 5 min of topical prostaglandin administration, compatible with the release of preformed mucus. Such prostaglandin-stimulated increases in mucus thickness will improve the protective capacity of the adherent mucus gel. The thickness of the adherent mucus layer is not changed following topical exposure, in vivo 1 hr before measurement, to exogenous mucosal-damaging agents (eg, ethanol, indomethacin and taurocholate. However, since such damaging agents permeate the mucus gel, it appears to offer little initial protection to the underlying epithelium. The mucus barrier primarily guards against the natural aggressors acid and pepsin, protecting the epithelium and its repair following acute mucosal damage.

The influence of bisacodyl and deacetylbisacodyl on mucus secretion, mucus synthesis and electrolyte movements in the rat colon in vivo

The effect of the diphenolic laxatives bisacodyl and deacetylbisacodyl on mucus secretion and fluid, sodium and potassium net transport was studied in rat colon perfused in vivo. Mucus output in the effluent was determined as total protein-bound hexose. Deacetylbisacodyl was more potent than the parent compound and was used to investigate dose-response relationships. At a low concentration (0.1 mg/dl), mucus and potassium secretion were stimulated whereas sodium and fluid absorption were inhibited, or converted to secretion, only at higher concentrations (0.5–3.0 mg/dl). All effects were dose-dependent and reversible within 1 h. With longer lasting perfusion of deacetylbisacodyl, mucus appeared in two peaks, one initial peak and another after 4 h. The late peak contained newly synthetized glycoproteins as indicated by the incorporation of intravenously injected [ 14C]galactose. It is concluded that stimulation of mucus secretion and synthesis contributes to the laxative action of bisacodyl. The effects of low versus high concentrations suggests that part of the potassium secretion is due to mucus release.

Fertility studies in young and mature merino ewes: 1. Cervical mucus production

The production of cervical mucus was determined at six-hour intervals during oestrus in young ( 1 1 2 years old) and mature (3 to 7 years old) Merino ewes. The length of the cervix and the length of the cervical epithelium was also measured in similar ewes. Total weight of mucus secreted as well as secretion rate per unit of time was greater in mature ewes than young ewes. Production was maximal during the first six hours of oestrus and declined considerably after 12 hours in young and 18 hours in mature ewes. The cervix was significantly shorter in young ewes while the length of the cervical epithelium was not significantly different in young and mature. It was concluded that lower mucus production in young ewes is not related to lower mucus output per unit area.

Influence of osmolality, short chain fatty acids and deoxycholic acid on mucus secretion in the rat colon.

Mucus secretion into the rat colon has been measured in situ using a single perfusion technique. Protein, sialic acid and hexose concentrations in the perfusion solution were found to give reliable estimates of mucus output if samples were homogenized prior to analysis. Mucus output as indicated by an increase in the concentration of mucus constituents was higher when the solution was hypotonic (270 mosm . kg-1) or hypertonic (370 mosm . kg-1) than when isotonic solutions (320 mosm . kg-1) were used. The proportion of hexoses and sialic acid to protein was 23 and 14% at low, 23 and 11% at high osmolality, and 21 and 13% when isotonic solutions were used. Deoxycholic acid (DCA, 4 mmol . 1(-1)) increased the net secretion of mucus constituents 3 fold, whereas short chain fatty acids (SCFA) had no effect. Mucus composition during all treatments did not change significantly, even when stimulated with DCA. When mucus was released from the epithelial surface by previous perfusion with a DCA containing solution, net water and SCFA absorption rates and mucus output were significantly lowered for 2 to 3 h. However, no correlation between mucus secretion and SCFA absorption was found, indicating that a role for mucus as a diffusion barrier to SCFA is unlikely. Mucus output, which indicates the amount of mucus released from the epithelial surface, probably depends on the direction of net water movement, which follows the osmotic gradient between colon lumen and blood.

Pharmacological inhibition of chenodeoxycholate-induced fluid and mucus secretion and mucosal injury in the rabbit colon

The effects of various pharmacological agents on bile acid-induced fluid secretion, mucus secretion, and mucosal injury were investigated using a perfusion technique in rabbit colon. Atropine markedly reduced and carbachol potentiated the fluid secretion, mucus output, and mucosal damage observed during bile acid perfusion. In contrast, pretreatment of the colonic mucosa with lignocaine and parenteral administration of methysergide and somatostatin produced a modest reduction in the fluid secretory response without apparent effects on mucus output or mucosal damage. These results suggested that cholinergic agonists and antagonists influence the mucosal resistance to bile acid-induced injury possibly through their effects on mucus secretion. Increasing or decreasing mucosal resistance to the detergent effects of bile acids appeared to have marked effects on the magnitude of induced fluid secretion. A minor reduction in overall secretory response to bile acids was also apparent with agents not influencing mucus secretion or mucosal injury.

Relationship between Mucus Output and Active Cl− Secretion in Cat Tracheal Epithelium

We wanted to know how the fluid component of tracheal mucous gland secretions is produced. One possibility is that, as in other epithelia, fluid movement is secondary to transepithelial active Cl− secretion.

Stimulation of mucus output from rat colon in vivo

Sodium chloride (155 mM) and N-acetyl cysteine (6 mM) were recirculated through the colons of anaesthetized rats. Mucus accumulated in the perfusion fluid which was changed at intervals to allow mucus output to be estimated by measurement of hexose. The output of mucus could be stimulated by intravenous administration of the cholinergic drugs carbachol and bethanechol; this effect was inhibited by atropine. Mucus output could also be stimulated by intravenous 5-hydroxytryptamine. This was not a muscarinic cholinergic effect because atropine did not prevent it. Neither did methysergide inhibit it; but chlorpromazine did. Precursors of 5-hydroxytryptamine, 5-hydroxytryptophan and L-tryptophan, also stimulated mucus output if given in high dosage. The results suggest that in this preparation muxus output can be stimulated by two distinct mecahnisms, one cholinergic, the other involving 5-hydroxytryptamine and perhaps 5-hydroxytryptophan.

Control of Mucus Secretion and Ion Transport in Airways

The output of secretions from the airway submucosal glands is regulated by vagal efferent nerves. Stimulation of cough receptors increases mucus output reflexly via the vagus nerves. Adrenergic agonists increase submucosal gland secretions in some species, which indicates that adrenergic receptors are present in these cells. However, evidence for adrenergic nervous pathways to the glands is limited. Irritants and drugs stimulate secretion from epithelial cells by direct effects. There is also evidence that the secretion of epithelial cells can be stimulated by parasympathetic nervous pathways in birds but not in mammals. Active ion transport of Cl- toward the lumen and of Na+ toward the submucosa results in net ion movement toward the airway lumen in unstimulated tracheal epithelia. Drugs and mediators increase the net movement of ions toward the lumen. No agents have yet been found that increase net ion movement toward the submucosa. The link between ion transport and water secretion in airway epithelia, although speculative, seems likely in view of the evidence from other epithelia. Since airway epithelium is a "tight junction" epithelium, modification of the tight junction may alter the transepithelial movement of water and ions. We suggest that the depth and consistency of the periciliary layer of airway secretions determine the ability of the cilia to propel the mucoprotein gel and thereby modify mucociliary transport. To achieve this, secretion of mucus must be controlled separately from the secretion of water. Studies are needed to determine which of the specialized functions of the epithelial cells interact to regulate the clearance of secretions from the airway. Is the sol maintained by secretion and reabsorption of fluid across the epithelium? Does the sol move with the gel by ciliary action or does it remain stationary? Do changes in the epithelial tight junctions influence net water movement and thus indirectly alter the depth of the sol layer? To answer these questions, techniques are needed to study subunits of the airway, including isolated surface cells and submucosal glands; and sensitive methods are required to analyze the very small samples of secretions for glycoprotein and electrolyte content. Intracellular measurements of electrolyte concentrations and electrical potentials may help to elucidate the mechanisms of transepithelial ion and water movement. The control system for the production and removal of respiratory tract secretions may be altered in disease. For instance, chronic stimulation of cough receptors causes reflex secretion and may be the cause of the hyperplasia of submucosal glands and of the abnormal secretions that occur in chronic bronchitis and asthma (50, 58). The abnormally viscid mucus in cystic fibrosis may be due to a defect in Cl- transport, which provides too little water for both the gel and sol layers. These speculations are intended to identify areas for further research, which hopefully will reduce the morbidity and mortality in these common lung diseases.

Stimulation by intragastrically administered E2 prostaglandins of human gastric mucus output

Abstract. Prostaglandin E2 and 15(R)15 methyl prostaglandin E2 were instilled intragastrically to study gastric mucus output in healthy male subjects during an infusion of pentagastrin. Mucus was measured by determining total, free, and bound N‐acetyl neuraminic acid (NANA) in gastric recoveries. NANA is a sialic acid located at the end terminals on the carbohydrate chains of mucus glycoprotein. It contributes to viscosity and prevents enzymatic degradation of mucus.The methyl analogue of prostaglandin E2 increased the gastric output of NANA and inhibited gastric acid secretion in a dose‐dependent fashion. NANA produced in response to the analogue was bound to mucus glycoprotein. Prostaglandin E2 increased the output of NANA without affecting the gastric acid secretion. Both prostaglandin E2 and its methyl analogue increased volumes, pH, and NANA content of gastric aspirates withdrawn prior to start of the pentagastrin infusion, indicating a stimulation of the alkaline gastric secretion.The results show that oral E2 prostaglandins have dual effects on gastric secretion, and that their ability to stimulate mucus production is not secondary to gastric acid inhibition. Further studies are needed to examine whether their effect is mainly to increase the incorporation of NANA into mucus glycoproteins, or to stimulate the release and/or production of gastric mucus, and also to quantitate the gastric nonparietal secretion.The stimulatory properties of E2 prostaglandins on gastric mucus and alkaline secretion may be one mechanism by which they protect the gastric mucosa against experimentally induced damage.

Effects of bile acids on mucus secretion in the dog colon.

The effects of unconjugated bile acids on colonic mucus production have been studied in the dog. Isolated segments of both ascending and descending colon were simultaneously perfused with either chenodeoxycholic, deoxycholic or cholic acid and the mucus production estimated from the total hexose output. Each bile acid produced a significant increase in mucus output in both the right and left colonic segments. There were no differences between the right and left colon in terms of mucus output for any of the bile acids studied. Deoxycholic had a greater effect than chenodeoxycholic which had a greater effect than cholic acid in colonic mucus production. Further, these effects on mucus secretion were completely reversible. In diarrhoea associated with disease or resection of the ileum, the effect of bile acids on mucus secretion may be as important as their effects on the inhibition of water and electrolyte absorption.

Derangements of biosynthesis, production and secretion of mucus in gastrointestinal injury and disease.

The derangements in production and secretion of gastric mucus consist of: 1) Quantitative changes in concentration and output of mucus; 2) Qualitative changes in its composition; 3) Increased shedding of the mucus-containing surface epithelial cells and excessive extrusion of the mucus from the cells; 4) Abnormalities in the biosynthesis of glycoproteins of the mucus.