Mucus Volume Research Articles

Endothelin‐1 inhibits pre‐stimulated tracheal submucosal gland secretion and epithelial albumin transport

1. Endothelin-1 potently contracts smooth muscle, including that in the airways. However, its effect on airway mucosal function has not so far been studied. 2. We have used the ferret whole trachea in vitro to examine the effect of endothelin-1 on tracheal smooth muscle tone, transepithelial potential difference (p.d.), submucosal gland secretion (including lysozyme secretion from serous cells) and active epithelial albumin transport. In addition we have examined the effects of endothelin on submucosal gland secretion and albumin transport pre-stimulated with the muscarinic agonist methacholine and the alpha-adrenoceptor agonist phenylephrine. The effects of the Ca2+ channel blocker nifedipine on the responses to endothelin have also been assessed. 3. Endothelin (0.1-100 nM) produced concentration-dependent increases in intraluminal tracheal pressure indicating smooth muscle contraction, and in the negativity of the transepithelial p.d. These effects were partially inhibited by nifedipine (10 microM). 4. Endothelin (0.01-100 nM) had no significant effect on baseline rates of mucus, lysozyme or albumin outputs, but produced concentration-dependent reductions in maintained methacholine- and phenylephrine-induced mucus, lysozyme and albumin outputs. In general endothelin was more potent against methacholine-induced effects. All of the concentration-response curves for endothelin were shallow and some appeared to be biphasic, suggesting the possibility of more than one mechanism of action of endothelin. 5. The effects of endothelin (at concentrations greater than 1 nM) on phenylephrine-induced mucus volume, lysozyme and albumin outputs were significantly inhibited by nifedipine. Similarly the effect of endothelin (greater than 1 nM) on methacholine-induced mucus volume and albumin outputs (but not lysozyme output) was attenuated by nifedipine. Similarly the effect of endothelin (>1 nM) on methacholine-induced mucus volume and albumin outputs (but not lysozyme output) was attenuated by nifedipine. The effects of endothelin (at concentrations <1 nM) on methacholine and phenylephrine-induced responses were generally not affected by nifedipine.6. Thus, endothelin contracts ferret tracheal smooth muscle and increases transepithelial p.d. at least in part by opening dihydropyridine-sensitive Ca2+ channels. Endothelin does not directly stimulate submucosal gland secretion or epithelial albumin transport, but inhibits methacholine- and phenylephrineinduced secretion and transport. The inhibitory effects produced by higher concentrations of endothelin may be mediated partially by activation of dihydropyridine-sensitive Ca2+ channels, although the explanation for this is not clear. The mechanism of action of endothelin in attenuating stimulated secretion and epithelial transport at lower concentrations is unknown.

Increased Urinary Mucus Production: A Sequela of Cystography following Enterocystoplasty

Early postoperative urinary mucus secretion was evaluated in 13 consecutive patients who underwent lower urinary tract reconstruction with incorporation of bowel segments, and the effect of intravesical infusion of sodium diatrizoate and meglumine diatrizoate in aqueous solution (Urografin 30%) was assessed. The mean volume of urinary mucus extracted before and immediately after cystography increased from 1.4 to 9.6ml., respectively (p <0.0001). We conclude that mucus excretion increases significantly immediately following cystography during the early postoperative period. During that critical time cystography may cause potential hazards of mucus retention and catheter obstruction, which should be anticipated and treated promptly.

The effects of calcitonin gene‐related peptide on submucosal gland secretion and epithelial albumin transport in the ferret trachea in vitro

1. We have examined the effect of calcitonin gene-related peptide (CGRP) on basal mucus volume, lysozyme and albumin outputs from the ferret whole trachea in vitro, and on the outputs produced by methacholine and substance P (SP). We have also examined the effect of inhibiting neutral enkephalinase with thiorphan on the responses to CGRP. 2. CGRP (1-100 nM) produced small concentration-dependent increases in basal mucus volume, lysozyme and albumin outputs. These effect of CGRP were enhanced by thiorphan. The increases in basal outputs with CGRP and the potentiation by thiorphan were considerably less than previously observed with SP and neurokinin A (NKA). CGRP had no significant effect on potential difference (PD) across the trachea. 3. CGRP produced a concentration-dependent inhibition of methacholine- and SP-induced lysozyme output but a concentration-dependent increase in methacholine- and SP-induced albumin output. The effects of CGRP on methacholine-induced lysozyme and albumin outputs were enhanced by thiorphan. CGRP weakly inhibited methacholine-induced mucus volume output and weakly enhanced SP-induced mucus volume output. 4. Thus, CGRP weakly stimulates basal serous cell secretion and epithelial albumin transport, but does not alter epithelial integrity. CGRP inhibits the serous cell secretion due to methacholine or SP, but potentiates the epithelial albumin transport produced by these agents. The interaction between CGRP and other sensory neuropeptides or muscarinic agonists on airway submucosal glands and epithelium may be important in the normal airway and in inflammatory airway diseases where release of sensory neuropeptides is enhanced.

The effect of hydrogen peroxide on smooth muscle tone, mucus secretion and epithelial albumin transport of the ferret trachea in vitro

The effect of hydrogen peroxide (H 2O 2) was examined on baseline and on methacholine- and phenylephrine-stimulated smooth muscle tone, mucus volume and lysozyme outputs, and epithelial albumin transport of the ferret whole trachea in vitro. H 2O 2 (10 μM–10 mM) had no significant effect on tracheal smooth muscle tone but produced concentration-dependent increases in mucus volume, lysozyme and albumin outputs. The potential difference (P.D.) across the trachea was not changed by H 2O 2. Exposure of the trachea to H 2O 2 (1 mM) for 2 h reduced the smooth muscle contractions and lysozyme outputs due to methacholine (1 μM) and phenylephrine (10 μM). Methacholine-induced albumin output was significantly increased by H 2O 2 but that due to phenylephrine was not significantly affected. Exposure to H 2O 2 had no significant effect on the mucus volume output produced by methacholine or phenylephrine. Thus H 2O 2 directly stimulates submucosal gland secretion, including secretion from serous cells, and epithelial albumin transport across the ferret trachea but has no effect on tracheal smooth muscle tone. H 2O 2 reduces methacholine- and phenylephrine-induced smooth muscle contractions and serous cell secretion. H 2O 2 causes hyperresponsiveness of albumin output to methacholine but not to phenylephrine.

Mechanism of intragastric nicotine protection against ethanol-induced gastric injury

To elucidate the mechanism of intragastric nicotine protection against ethanol-induced gastric mucosal injury seen in a previous report and in our preliminary study, the following studies were performed. Rats were pretreated with naloxone (8 mg/kg intraperitoneal, 0.5 hr prior to study) to block opiate receptors; or capsaicin (125 mg/kg subcutaneous 10 days prior to study) to denervate the afferent sensory fibers; or indomethacin (2.5 mg/kg intragastric or 5 mg/kg subcutaneous, 1 hr prior to study) to inhibit endogenous prostaglandin synthesis. At 1-hr intervals, nicotine (4 mg/kg) or vehicle and 40% ethanol were then given intragastrically. Total gastric corpus mucosal lesion length was measured unbiasedly. In separate studies, gastric mucosal blood flow (GMBF) was assessed by hydrogen gas clearance before and after intragastric nicotine or vehicle; luminal mucus volume, gastric juice volume, and acid output were measured 1 hr after either intragastric nicotine or vehicle administration. The results showed that the acute protective effect of intragastric nicotine was associated with a significantly larger luminal mucus volume. It was not blocked by naloxone, capsaicin, or indomethacin. There was no increase in GMBF. The larger gastric residual volume did not account for the protection. We conclude that the mechanism mediating nicotine protection is unique and is independent of opiate receptors, capsaicin-sensitive afferent sensory nerve fibers, endogenous prostaglandin generation, or dilution of the injurious agent. The increase in luminal gastric mucus volume may contribute to the protective effect of intragastric nicotine against gastric mucosal injury produced by 40% ethanol.

Atropine treatment induced cholinergic supersensitivity at receptor and second messenger levels in the rat salivary gland

Physiological, biochemical and morphological correlates of chronic treatment of rats with the classical muscarinic antagonist atropine for 14 days (20 mg kg-1 day-1 s.c.) were studied in submandibular salivary glands. The amount of saliva collected from submandibular glands following a single injection of isoproterenol (30 mg kg-1 i.p.) was significantly larger and had higher protein concentration in rats treated with atropine than in saline-treated animals. In the glands of atropine-treated rats a conspicuous increase in the amount of rough endoplasmic reticulum (RER) along with a decrease in the mucous volume was observed in the acinus when examined by light microscopy. Several biochemical changes were observed in an enriched plasma membrane fraction from the submandibular gland of the atropine-treated rats: (1) an increase in the number of muscarinic antagonist binding sites (31 + 3.4%), (2) a decrease in the specific activity of basal adenylate cyclase, (3) a significantly lower Vmax of the adenylate cyclase in the presence of GTP (10 microM) and varying concentrations of Mg2+ (0-22.5 mM) with no apparent change in affinity of the enzyme for Mg2+ but (4) higher magnitude of stimulation in the presence of GTP (100 microM), vasoactive intestinal polypeptide (5 microM), isoproterenol (100 microM), NaF (10 microM) and forskolin (10 microM). There was however no change in the density of beta-adrenergic receptors upon atropine treatment. In tissue slices from the submandibular glands of atropine-treated rats we found lower basal cAMP levels (decrease 29 +/- 6.9%) and no significant change in the phosphatidylinositol breakdown stimulated by carbachol (10(-6) to 10(-4) M). It appears that chronic blockade of an inhibitory muscarinic input to the adenylate cyclase system is compensated by lowered adenylate cyclase activity. Phosphoinositide metabolism is not subject to the same adaptation, suggesting that cAMP may be the pivotal second messenger in the supersensitive salivary response.

Correlation of Gastric Mucous Volume with Levels of Five Prostaglandins after Gastric Mucosal Injuries by NSAIDs

After administration of NSAIDs (aspirin and indomethacin), chronological changes in gastric mucous volume were determined. These mucous volume changes were evaluated in relation to the development of gastric mucosal injuries. Furthermore, quantitative changes in five kinds of prostaglandins (PGs) in the gastric mucosa were measured after administration of NSAIDs. Gastric mucus volume was measured using a video image processor (VIP), and five kinds of PGs were fractionated by high-performance liquid chromatography (HPLC) and quantitatively determined by radioimmunoassay (RIA). We found that NSAIDs decrease the levels of five kinds of PGs to the same extent. Also, gastric mucous volume is decreased after administration of aspirin and increased after administration of indomethacin. Accordingly, it is possible that each NSAID has a different mechanism of producing the gastric mucosal injury and acts on gastric mucus in a different manner. There was no parallel in changes between gastric mucous volume and PG levels of the different PGs in the gastric mucosa after administration of NSAIDs.

Receptors mediating the effects of substance P and neurokinin A on mucus secretion and smooth muscle tone of the ferret trachea: potentiation by an enkephalinase inhibitor

1. The effects of substance P (SP) and neurokinin A (NKA) were examined on tracheal smooth muscle tone, mucus volume output, lysozyme output and albumin transport across the ferret in vitro whole trachea in the presence and absence of the enkephalinase inhibitor, thiorphan. 2. SP (0.001-3 microM) and NKA (0.01-10 microM) contracted the tracheal smooth muscle and increased mucus volume, lysozyme and albumin outputs into the tracheal lumen. The EC50 values for SP and NKA for all of the variables measured were significantly reduced, and all of the maximum responses were significantly enhanced by thiorphan (10 microM). 3. In the presence of thiorphan, SP (1 microM) and NKA (10 microM) produced albumin concentrations in the secreted mucus (8.9 and 7.2 micrograms microliters-1) which were greater than those in the submucosal buffer (4.2 micrograms microliters-1). 4. In the presence of thiorphan, NKA was approximately 5 times more potent than SP at contracting the tracheal smooth muscle. Conversely SP was 23, 15 and 22 times more potent than NKA at stimulating mucus volume, lysozyme and albumin outputs respectively. 5. Thus, there is neutral endopeptidase in the ferret trachea in vitro which cleaves exogenously applied SP and NKA, thereby reducing the magnitude and potency of their actions. SP and NKA contract the ferret tracheal muscle probably by an action at NK2 (or NK3)-receptors but stimulate mucus volume output, lysozyme output and albumin transport across the tracheal wall probably by an action on NK1 receptors.

Morphometric analysis of intraluminal mucus in airways in chronic obstructive pulmonary disease.

Mucus volume in both central and peripheral airways was assessed in 13 patients, six with chronic bronchitis (CB) and seven with chronic pulmonary emphysema (CPE), by morphologic quantitative measurement in autopsied lungs, and the results were compared with those from four control lungs (NL). The patients with CB and CPE had severe obstructive impairment that did not differ significantly between the two groups (FEV1%, mean 45% in CB and mean 49% in CPE). Mucous hypersecretion during clinical remission differed significantly between the CB and CPE groups (mean 80 ml/day in CB and mean 8 ml/day in CPE). The length of the airway basement membrane and the area of mucus were measured with a digitizing computer. The volume ratio of mucus to airway lumen, which was defined as the volume ratio of mucus to airway lumen calculated as a cylinder by the length of basement membrane, was regarded as the mucus occupying ratio (MOR). MOR was significantly higher in CB lungs (4.1 +/- 1.0% in central airways and 19.6 +/- 3.8% in peripheral airways, mean +/- SE) than in NL (0.3 +/- 0.1% in central airways and 0.6 +/- 0.3% in peripheral airways, respectively) in both central and peripheral airways (p less than 0.05 and p less than 0.01, respectively), whereas no significant increase in MOR was found in CPE lungs, compared with NL. Furthermore, peripheral airway MOR was significantly higher than that of central airways in CB lungs (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of polyethylene glycol 1540 and Witepsol H12 suppositories on the store of rectal mucus in the rat

The volume of rectal epithelial mucus was quantified histologically following a single suppository treatment. It was: unchanged by suppositories of Witepsol H12; reduced significantly by suppositories of PEG 1540 1, 6 and 24 h post-treatment but increased after 48 h.

The effect of filtration on absolute and differential cell counts in fluid obtained at bronchoalveolar lavage

We have studied the effects of filtering mucus from bronchoalveolar lavage (BAL) fluid on its cellular contents. We examined BAL fluid from 18 patients without excessive endobronchial mucus, and from three patients with bronchiectasis. In the non-bronchiectatic subjects there was a fall of 18% in mean absolute cell count from 2.66 +/- SD 1.9 x 10(9) l-1 to 2.18 +/- 1.4 x 10(9) l-1 (P less than 0.05) as a result of filtration. This was due to a selective loss of macrophages and there were no significant changes in the absolute numbers of either lymphocytes or neutrophils. The differential macrophage count fell from a mean of 82 +/- 14% to 76 +/- 16%, while the mean differential lymphocyte count rose from 14 +/- 7% to 19 +/- 9% and the mean differential neutrophil count increased slightly from 4 +/- 4% to 5 +/- 4%. In the three patients with bronchiectasis the absolute cell counts were grossly raised, due almost entirely to an excess of neutrophils. In these patients, filtration reduced the absolute macrophage count by 61% and the absolute neutrophil count by 27%. Overall, change in absolute cell count correlated significantly with mucus volume (r = 0.76, P less than 0.05). Removal of mucus by filtration affects absolute cell count and may have a selective effect on cell numbers. If filtration of BAL fluid is unavoidable, its effect on cell counts should be clearly established if data from different centres are to be meaningfully compared.

A Study on Gastric Ulcers Induced by Long-Term Fasting in Rats

The present study was performed to investigate the roles of intragastric pH and PAS positive mucus as to the incidence of gastric ulcers after long-term fasting in rats. Gastric ulcers in the forestomach and corpus were found at 4 and 6 days after fasting, respectively. The intragastric pH was significantly reduced at 1, 2, 3, 4, 6 and 7 days after fasting, but tended to have returned to control levels at 8 days. PAS positive mucus was significantly increased at 2 to 7 days, but there was no significant change at 8 days. From these results, it seems that the aggressive factor is not involved, but attenuation of the defensive factor is important as to the incidence of this type of ulcer. As one of the causes of this attenuation, a decrease in the gastric mucus volume was suggested.

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.

Influence of estrogens on vascular transudation and mucus production in the rabbit endocervix

The manner in which estrogens mediate cyclical changes in the viscoelastic properties and volume of cervical mucus is unclear. To identify the response to estrogens of each of the major mucus components (mucin[s], soluble proteins, and small electrolytes and water), the authors quantitated their accumulation rates before and during estrogen stimulation in the rabbit. Circulating radiolabeled markers (35S-sulfate and 131I-albumin) were used to monitor the incorporation of small and large molecular weight intravascular substances into the cervical mucus. The accumulation rate of mucins was unaffected by exogenous estrogen administration, despite significant increases in mucus volume. This increase in mucus volume was attributed to a significantly increased transudation of water and small electrolytes increasing mucus hydration as early as the first 2 hours of estrogen administration. Water, small electrolytes, and soluble proteins significantly increased during the third and fourth hours of estrogen administration, not only when compared with the unstimulated basal levels, but also when compared with the levels found during the first 2 hours of estrogen administration. No significant change occurred in mucin production, while significant changes occurred in the accumulation of proteins and small electrolytes, whether estrogen was given initially or terminally in the experiment protocol.

The effects of peptides and mediators on mucus secretion rate and smooth muscle tone in the ferret trachea.

The effects of a number of peptides and mediators were measured on the secretion rate of tracheal mucus and tracheal smooth muscle tone in the ferret in vitro whole trachea. The comparison of secretion rate and smooth muscle tone, measured simultaneously in the same preparation, shows that there are wide differences in sensitivity between the two systems; there appears to be no relationship between mucus volume output and smooth muscle contraction. The comparison of mucus secretion rate and glycoprotein output in other models and species to these drugs in the same concentrations indicates that there may be mucus glycoprotein output without an increase in volume output.

Cigarette Smoking and Respiratory Tract Infection

Although not conclusive, several lines of evidence suggest that cigarette smoking alters the respiratory tract's ability to defend itself from infection. Some subjects with chronic bronchitis have colonization of the lower respiratory tract with bacteria. Both patients with chronic respiratory disease and healthy smokers appear to have a higher frequency of respiratory infections and an increased severity of symptoms when infected. Children exposed passively to cigarette smoke have higher rates of respiratory illnesses. Yet the marked variability in the incidence of infection in the smoking population suggests that there are subtle factors that predispose some smokers to more risk of infection than others. Cigarette smoking is associated with alterations in mechanisms of the host defense system, even in asymptomatic individuals (summarized in Table 3). Ciliary function is impaired, mucous volume is increased, humoral response to antigens altered, and quantitative and qualitative changes in cellular components occur. Some of these alterations in host defense mechanisms are dose related; others revert to normal after smoking cessation. Yet, it is unknown if one or all of these alterations cause any significant compromise of host defense or if other factors, as yet unidentified, may be important. Answers to these questions await a more thorough elucidation of normal host defense function.

Acid particles and the tracheobronchial region of the respiratory system--an "irritation-signaling" model for possible health effects.

This paper explores some detailed mechanistic hypotheses for the possible action of acid particles on the tracheobronchial region of the human respiratory system. Because of the buffering capacity and volume of mucus produced per day it appears doubtful that ordinary ambient exposures to acid particles could markedly change the overall pH of tracheobronchial mucus considered as a whole. However, it is possible that individual acidic particles could contain enough acid to deliver localized irritant signals that could be the triggers for enhanced mucus secretion and cell division in sensitive portions of the bronchial tree, and thereby contribute to the processes involved in chronic bronchitis. Depending on the exact pH depression required for a signal to be perceived by the tracheobronchial epithelium, the acid content of the incoming particles per unit weight, and the effect of neutralization by ammonia in the upper respiratory tract, the minimum size of an acidic particle required to deliver a perceptible signal might range from about 0.4 to 0.7 microns for portions of the epithelium that are frequently swept by 4-micron mucus droplets. Since particle number per unit weight declines dramatically with increasing particle size, the most potent fraction of particles in terms of signals deliveredmore » per /sup +/g/m/sup 3/ is likely to be just above the minimum size that is needed to produce an effective signal. The model developed here makes predictions of the relative potency of particles of different size and acid delivery capacity that could be tested in both experimental animal systems and human epidemiological studies.« less

Changed control of cervical secretion from infertile ewes previously exposed to oestrogenic clover pasture.

The amount of cervical mucus recovered from control ovariectomized ewes increased with increasing doses of oestradiol benzoate (OB), while the maximum Spinnbarkeit of mucus occurred at an intermediate dose of OB. Neither the amount nor the Spinnbarkeit of mucus varied with the dose of OB in ewes with permanent infertility caused by grazing oestrogenic pasture (clover-affected ewes). Furthermore, the increase in Spinnbarkeit of cervical mucus seen in normal ewes treated over a 3-day period with OB or with implants containing oestradiol did not occur in affected ewes. In control ewes treated repeatedly with OB, production of mucus declined within 5 days, but no change in secretion was detectable in clover-affected ewes. Therefore, neither the amount nor the duration of oestrogenic stimulation affected the cervical mucus in ewes with clover disease. Affected ewes produced more mucus than did controls in the absence of oestrogenic stimulation. It is concluded that the relatively normal volume of mucus in affected ewes treated with OB results largely from autonomous production. The Spinnbarkeit does not increase in these ewes because the ability of the cervix to respond to oestrogen is impaired.

Effects of calcitonin on elemental distribution and ultrastructure of rat submandibular gland acinar cells.

The effect of calcitonin on rat submandibular gland acinar cells was investigated by X-ray microanalysis and electron microscopy. Calcitonin caused a transient increase of the cellular calcium and magnesium concentration, but did not affect the intracellular concentration of other electrolytes. The relative volume of intracellular mucus increased from 45% in control glands to 72% at 6 h after administration of calcitonin. Calcitonin caused an inhibition of the cellular response of the acinar cells to beta-adrenergic and cholinergic agonists. The changes in elemental composition and ultrastructure of the gland cells are probably due to inhibition of mucus release from the cells.

Changes in volume of stored mucus in pit and surface cells during their maturation and migration in the antral mucosa of the mouse.

In antral mucosa of the mouse stomach, the volume of mucus in mucous cells was measured morphometrically to determine whether this value changes during cell migration from the base of the pit to the surface. Both the volume density of mucous granules (the fraction of cell volume occupied by the granules) and the volume of intracellular mucus were reduced to about half in surface cells compared with those of upper pit cells. This indicates that mucus secretion is substantial during the later part of the lifespan of these cells, and is not due simply to the shedding of senescent cells.