Soluble Mucus Research Articles

Evaluating mucus exudation dynamics through isotopic enrichment and turnover of skin mucus fractions in a marine fish model.

Fish skin mucus is composed of insoluble components, which form the physical barrier, and soluble components, which are key for interrelationship functions. Mucus is continuously secreted, but rates of production and exudation are still unknown, as are the underlying mechanisms. Using stable isotope analysis, here, we evaluate skin mucus turnover and renewal in gilthead sea bream, separating raw mucus and its soluble and insoluble fractions. Isotopic abundance analysis reveals no differences between mucus and white muscle, thus confirming mucus samples as reliable non-invasive biomarkers. Mucus production was evaluated using a single labelled meal packaged in a gelatine capsule, with both 13C and 15N, via a time-course trial. 13C was gradually allocated to skin mucus fractions over the first 12h and was significantly (4-fold) higher in the soluble fraction, indicating a higher turnover of soluble mucus components that are continuously produced and supplied. 15N was also gradually allocated to mucus, indicating incorporation of new proteins containing the labelled dietary amino acids, but with no differences between fractions. When existent mucus was removed, dietary stable isotopes revealed stimulated mucus neoformation dependent on the components. All this is novel knowledge concerning skin mucus dynamics and turnover in fish and could offer interesting non-invasive approaches to the use of skin mucus production in ecological or applied biological studies such as climate change effects, human impact, alterations in trophic networks or habitat degradation, especially of wild-captured species or protected species.

Fugu, Takifugu ruberipes, mucus keratins act as defense molecules against fungi

Keratin is a cytoskeletal protein that constitutes the intermediate filament. Its distribution is restricted to epithelial tissues in mammals, but is wider in fish. An interesting feature of fish keratin is that it is abundant in the cutaneous mucus. However, the biological function of keratin in the mucus has not been explored. In the present study, we hypothesized that mucus keratins of fugu Takifugu rubripes function as antimicrobial molecules. To verify this hypothesis, we first identified all of the keratins expressed in the epidermis and present in mucus. Five of 15 keratins including Tr-K4 expressed in the epidermis were identified in the mucus. Subsequently, we examined the interaction of keratin molecules present in fugu mucus with yeast. Affinity chromatography using yeast as a carrier and subsequent LC–MS/MS analysis revealed that three types of keratin were bound to the yeast. Furthermore, yeast incubated with fugu mucus was agglutinated, and this was inhibited by anti-recombinant Tr-K4 (rTr-K4) antibody. Immunohistochemical analysis also revealed that keratin was attached to the surface of agglutinated yeasts. These findings indicate that mucus keratin agglutinates yeast. Furthermore, we found insoluble clumps in fugu mucus, which were mainly comprised of keratin. After incubation of yeast with soluble mucus fraction, insoluble clumps incorporating yeast were formed. This observation suggests that fugu mucus keratin sequesters microbes into insoluble clumps, which are eventually eliminated from the mucus. Here, we present our finding of the novel function of keratin as a defense molecule in fish mucus.

Soluble mucus component CLCA1 modulates expression of leukotactic cytokines and BPIFA1 in murine alveolar macrophages but not in bone marrow-derived macrophages

The secreted airway mucus cell protein chloride channel regulator, calcium-activated 1, CLCA1, plays a role in inflammatory respiratory diseases via as yet unidentified pathways. For example, deficiency of CLCA1 in a mouse model of acute pneumonia resulted in reduced cytokine expression with less leukocyte recruitment and the human CLCA1 was shown to be capable of activating macrophages in vitro. Translation of experimental data between human and mouse models has proven problematic due to several CLCA species-specific differences. We therefore characterized activation of macrophages by CLCA1 in detail in solely murine ex vivo and in vitro models. Only alveolar but not bone marrow-derived macrophages freshly isolated from C57BL6/J mice increased their expression levels of several pro-inflammatory and leukotactic cytokines upon CLCA1 stimulation. Among the most strongly regulated genes, we identified the host-protective and immunomodulatory airway mucus component BPIFA1, previously unknown to be expressed by airway macrophages. Furthermore, evidence from an in vivo Staphylococcus aureus pneumonia mouse model suggests that CLCA1 may also modify BPIFA1 expression in airway epithelial cells. Our data underscore and specify the role of mouse CLCA1 in inflammatory airway disease to activate airway macrophages. In addition to its ability to upregulate cytokine expression which explains previous observations in the Clca1-deficient S. aureus pneumonia mouse model, modulation of BPIFA1 expression expands the role of CLCA1 in airway disease to involvement in more complex downstream pathways, possibly including liquid homeostasis, airway protection, and antimicrobial defense.

Goblet Cell-Derived CLCA1 Protein: A Soluble Mucus Component with Antimicrobial Properties

Goblet Cell-Derived CLCA1 Protein: A Soluble Mucus Component with Antimicrobial Properties

The Rat IgGFcγBP and Muc2 C-Terminal Domains and TFF3 in Two Intestinal Mucus Layers Bind Together by Covalent Interaction

BackgroundThe secreted proteins from goblet cells compose the intestinal mucus. The aims of this study were to determine how they exist in two intestinal mucus layers.Methodology/Principal FindingsThe intestinal mucosa was fixed with Carnoy solution and immunostained. Mucus from the loose layer, the firm layer was gently suctioned or scraped, respectively, lysed in SDS sample buffer with or without DTT, then subjected to the western blotting of rTFF3, rIgGFcγBP or rMuc2. The non-reduced or reduced soluble mucus samples in RIPA buffer were co-immunoprecipitated to investigate their possible interactions. Polyclonal antibodies for rTFF3, the rIgGFcγBP C-terminal domain and the rMuc2 C-terminal domain confirmed their localization in the mucus layer and in the mucus collected from the rat intestinal loose layer or firm layer in both western blot and immunoprecipitation experiments. A complex of rTFF3, which was approximately 250 kDa, and a monomer of 6 kDa were present in both layers of the intestinal mucus; rIgGFcγBP was present in the complex (250–280 kDa) under non-reducing conditions, but shifted to 164 kDa under reducing conditions in both of the layers. rMuc2 was found mainly in a complex of 214–270 kDa under non-reducing conditions, but it shifted to 140 kDa under reducing conditions. The co-immunoprecipitation experiments showed that binding occurs among rTFF3, rIgGFcγBP and rMuc2 in the RIPA buffer soluble intestinal mucus. Blocking the covalent interaction by 100 mM DTT in the RIPA buffer soluble intestinal mucus disassociated their binding.Conclusions/SignificanceRat goblet cell-secreted TFF3, IgGFcγBP and Muc2, existing in the two intestinal mucus layers, are bound together by covalent interactions in the soluble fraction of intestinal mucus and form heteropolymers to be one of the biochemical mechanisms of composing the net-like structure of mucus.

Biodegradable Microspheres Based on Gelatin-Porcine Mucin Admixtures: in Vitro and in Vivo Delivery Studies

Soluble mucus glycoprotein (S-mucin) processed from the small intestines (ileal region) of freshly slaughtered pigs via homogenization, dialysis, centrifugation and lyophilization and their admixtures with type B gelatin were used to prepare cefaclor-loaded microspheres by the emulsification-crosslinking method. The microspheres were evaluated for the in vitro delivery of cefaclor in both simulated intestinal fluid (SIF) without pancreatin (pH 7.4) and simulated gastric fluid (SGF) without pepsin (pH 1.2). Results obtained indicated that the microspheres formulated were highly mucoadhesive and that release of cefaclor in both release media was non-Fickian and was much higher and more rapid in SGF than in SIF and from microspheres based on gelatin alone when compared to those based on gelatin-procine mucin admixtures. The mean area under the plasma level versus time curves (AUC) was shown to be dependent on the formulation with values of 172.3 mug.h/ml for the control, 278.5 mug.h/ml for microspheres based on gelatin only and 353.0 mug.h/ml for microspheres formulated with equal parts of gelatin and mucin indicating that the rectal route may provide a therapeutically viable alternative to the oral route for the delivery of cefaclor. Further indications also emerged of a possibility of site-specific delivery of cefaclor to the small intestine through a careful selection of gelatin type and porcine mucin admixtures prior to formulation of the microspheres. On the whole, the inclusion of S-mucin in the composition of the microspheres had an enhancer effect on the release and rectal bioavailability of cefaclor which may be exploited in the design of a rectal delivery system of the drug.

Effects of Ya-hom on the gastric secretion in rats

The effects of Ya-hom, Thai traditional recipe, on gastric-secretory function was evaluated to verify its use for stomach discomfort treatment. The actions of Ya-hom on the gastric acid, pepsin and mucus secretions were studied in histamine- and carbachol-induced gastric fistula rats. After the first hour of collection, histamine (10 mg/kg, intramuscular injection) or carbachol (20 μg/kg, intravenous injection) were injected to stimulate gastric secretion, and water or redissolved lyophilized Ya-hom extract (0.5, 1, 2 and 4 g/kg) were intraduodenally injected. The gastric samples were collected every hour for 5 h, at the end of which, the glandular part of the stomach was assayed for the visible mucus content. Ya-hom inhibited both histamine- and carbachol-induced gastric acid, pepsin and soluble mucus secretions in a dose-dependent manner. Ya-hom had a lower maximum inhibition on the acid-stimulating effects of the histamine than that of carbachol. Ya-hom had higher maximum inhibition on the pepsin and soluble mucus-stimulating effects of histamine than that of carbachol. Ya-hom also had a higher elevated effect on histamine-induced visible mucus than that of carbachol. This study reveals that Ya-hom inhibits the stimulatory effects of histamine and carbachol on the acid, pepsin and soluble mucus secretion but potentiates the visible mucus secretion. Attenuating gastric secretion by secretagogues and increasing gastric barrier effects are parts of Ya-hom’s action on stomach discomfort treatment.

Effects of Aloe preparation on the histamine-induced gastric secretion in rats

The effects of Aloe preparation containing 80% Aloe gel on the gastric acid, pepsin and mucus secretion were evaluated in histamine-induced gastric fistula model in rats by comparison to the effects of placebo and fresh Aloe gel. Aloe preparation and placebo at a dose of 8 ml/kg inhibited gastric acid but stimulated pepsin secretory rates. On the other hand, fresh Aloe gel at a dose of 6.4 ml/kg prolonged histamine stimulatory effects on the gastric acid secretion while it inhibited gastric pepsin secretion. Both Aloe preparation and placebo increased soluble mucus secretory rate in a dose-dependent manner whereas fresh Aloe gel had no effect. The Aloe preparation and placebo at a dose of 8 ml/kg increased the gastric visible mucus content while fresh Aloe gel slightly increased the visible mucus content. This study reveals that fresh Aloe gel prolonged the effects of histamine-stimulated acid secretion and inhibits pepsin secretion in histamine-treated rats. The Aloe preparation inhibited gastric acid, stimulated pepsin and mucus secretion. However, there were no difference in the secretory rates of Aloe preparation and placebo-treated rats at the same doses. This result indicates that the observed effects of Aloe preparation was mostly due to other compositions of the preparation rather than Aloe gel itself. Since the highest dose of Aloe gel preparation used in the present study was limited by the volume of the instillated solution in gastric fistula model, the effects of Aloe vera gel were not able to be observed in the present study might be due to the inadequate dose of the preparation.

Influence of portal hypertension on secretion of gastric mucus in rats.

To assess the effect of portal hypertension on gastric adherent and soluble mucus in rats. Experimental study. Teaching hospital, Taiwan. 30 male Wistar rats. Portal hypertension was induced experimentally by partial ligation of the portal vein in 20 male Wistar rats: ten rats were examined after 4 weeks and the remaining 10 after 8. Another group of 10 rats (controls) had sham operations. Portal pressure, the severity of gross gastric mucosal lesions, and measurement of gastric adherent and soluble mucus. The portal pressure and the gross mucosal damage differed significantly between the experimental and the control groups (p < 0.01). There was significantly less gastric adherent mucus in the two experimental groups than in the control group (p = 0.002 and <0.001, respectively), whereas there was no significant differences in the amount of gastric soluble mucus (p = 0.5 and 0.1, respectively). The reduction in the gastric adherent mucus was closely related to the increase in portal pressure (p < 0.001) and the severity of portal hypertension-induced gastropathy (p < 0.001). Gastric adherent mucus may have an important role in the pathogenesis of portal hypertensive gastropathy, and its protective capacity is reduced by portal hypertension, as indicated by the decrease in gastric adherent mucus.

Effects of sodium fluoride on water and acid secretion, soluble mucus and adherent mucus of the rat stomach.

Chronic and acute ingestion of fluoride may lead to both structural and functional alterations of the gastric mucosa. The aim of this study was to investigate the effects of sodium fluoride on gastric secretion and mucosal barrier. Filling the rat stomach for 1 h with sodium fluoride (5 and 20 mmol/L) induced an increase in fluid, fucose and galactose output. This effect was accompanied by a marked pH-dependent reduction of titratable acidity of the lumen. The amount of Alcian blue bound to adherent mucus was reduced in a pH-independent manner by sodium fluoride. The absence of a correlation between soluble glycoproteins and adherent mucus suggests that sodium fluoride does not stimulate mucus secretion, but rather acts as a barrier-breaking agent by its accumulation, together with acid, into the mucosa.

Influence of L-365,260, a CCK-B/Gastrin Receptor Antagonist, on Tetragastrin- Stimulated Mucin Metabolism in Rat Gastric Mucosa

The effect of L-365,260, a CCK-B/gastrin receptor antagonist, on gastric mucus metabolism induced by tetragastrin was investigated in rats. In vivo application of L-365,260 at a dose of 3 mg/kg p.o. significantly reduced the tetragastrin (12 μg/kg s.c.)-stimulated gastric acid secretion, but 0.3 mg/kg of L-365,260 did not affect the gastric acid secretion induced by the tetragastrin administration. A single administration of 12 μg/kg of tetragastrin caused an increase in gastric mucin content in the soluble mucus (175% of control), the mucus gel (155% of control) and the surface mucosa (125% of control). L-365,260 at the doses of 0.3 and 3 mg/kg considerably inhibited the tetragastrin-induced mucus secretion in the soluble mucus (70–80% of tetragastrin) and the mucus gel (45–70% of tetragastrin) and resumed the mucus accumulated in the surface mucosa to the control situation (80% of tetragastrin). In the in vitro incubation system of rat gastric mucosa, L-365,260 (0.1–10 μmol/l) caused no significant change in gastric mucin synthesis. An in vivo study also showed that the increase in total gastric mucin content and the distributional changes in mucin content induced by 12 μg/kg of tetragastrin reverted with 3 mg/kg of L-365,260 pretreatment to the control situation. It is evident from these results that the CCK-B/gastrin receptor is involved in the mechanism of the stimulation of mucus secretion and/or mucus accumulation in rat gastric mucosa and not directly concerned with the action of gastrin-induced gastric acid secretion.

The regulation of mineral absorption in the gastrointestinal tract.

The absorption of metal ions in the mammalian single-stomached gut is fortunately highly selective, and both luminal and tissue regulation occur. Initially, assimilation of metal ions in an available form is facilitated by the intestinal secretions, chiefly soluble mucus (mucin) that retards hydrolysis of ions such as Cu, Fe and Zn. Metal ions then bind and traverse the mucosally-adherent mucus layer with an efficiency M+ > M2+ > M3+. At the mucosa Fe3+ is probably uniquely reduced to Fe2+, and all divalent cations (including Fe2+) are transported by a membrane protein (such as divalent cation transporter 1) into the cell. This minimizes absorption of toxic trivalent metals (e.g. Al3+). Intracellular metal-binding molecules (such as mobilferrin) may be present at the intracellular side of the apical membrane, anchored to a transmembrane protein such as an integrin complex. This mobilferrin would receive the metal ion from divalent cation transporter 1 and, with part of the integrin molecule, transport the metal to the cytosol for safe sequestration in a larger complex such as ferritin or 'paraferritin'. beta 2-Microglobulin and HFE (previously termed human leucocyte antigen H) may be involved in stabilizing metal mobilferrin-integrin to form this latter complex. Finally, a systemic metal-binding protein such as transferrin may enter the antiluminal (basolateral) side of the cell for binding of the sequestered metal ion and delivery to the circulation. Regulatory proteins, such as HFE, may determine the degree of ion transport from intestinal cells to the circulation. Gradients in pH and perhaps pCa or even pNa could allow the switching of ions between the different transporters throughout this mechanism.

A correlative study on the mechanism of adaptive cytoprotection against ethanol-induced gastric lesion formation in rats.

The protective effect of mild irritants against the subsequent gastric injury induced by necrotizing agents has been termed 'adaptive cytoprotection'. In this study, the possible pathway and mechanisms of adaptive cytoprotection induced by 20% ethanol were investigated. An ex-vivo gastric chamber preparation was used. The gastric mucosa was exposed to 20% ethanol before subsequent administration of 100% ethanol 15 min later. Subdiaphragmatic vagotomy or drug pretreatment was carried out in order to elucidate the mechanisms of adaptive cytoprotection by 20% ethanol. The results showed that 20% ethanol pre-exposure significantly protected the gastric mucosa against damage caused by 100% ethanol. This protective action was completely abolished by atropine or lidocaine pretreatment, whereas vagotomy and hexamethonium failed to have a significant influence. The cytoprotective effect, however, was independent of the gastric secretory volume, titratable acid content, luminal soluble mucus level and gastric mucosal blood flow. Exposure of only half the gastric mucosa to the mild irritant resulted in the protection of both sides of the mucosa. All these findings indicate that the adaptive cytoprotection of 20% ethanol involves the participation of chemoreceptors and muscarinic receptors in the gastric mucosa. An internal enteric reflex arc, with transmission of signals within the gastric mucosa, may also contribute to the cytoprotective process of the mild irritant.

Comparison of the mucus glycoproteins present in the different layers of rat gastric mucosa

1. 1. Applying a newly developed separation method, mucus glycoproteins (mucins) present in the different layers of gastric mucosa in rats were studied. 2. 2. Distributions of mucin in the four layers of gastric mucosa expressed as mg mucin hexose per animal are: deep mucosa of corpus, 705; deep mucosa of antrum, 163; surface mucus, 421; mucus gel, 30; and soluble mucus, 173. 3. 3. Relatively low molecular sugar chains, having a small amount of neutral sugars, are rich in the deep corpus and deep antral mucin. 4. 4. Higher molecular size carbohydrate chains, rich in fucose and galactose, are abundant in the surface mucus and mucus gel-derived mucin.

Effects of the muscarinic receptor agonist carbachol and/or antagonist pirenzepine on gastric mucus secretion in rats.

The effects of the muscarinic agonist carbachol on the secretion and accumulation of gastric mucus glycoprotein (mucin) were examined. Gastric mucin obtained from the soluble mucus, adherent mucus gel, and surface mucosal and deep mucosal layer was isolated and quantified. One hour after the subcutaneous administration of carbachol (0.08-80 micrograms/kg body weight) the deep corpus mucin content had decreased significantly (75% of control), corresponding to an increase (120% of control) in the soluble mucin content with 0.8 microgram/kg of carbachol treatment. These changes were counteracted by 10 mg/kg of pirenzepine (selective M1 antagonist) pretreatment. On a single administration of 10 mg/kg of pirenzepine, deep corpus mucin tended to increase, and soluble mucin decreased significantly (49% of the control). These two drugs failed to cause any significant change in the mucin content of the surface and antral deep mucosa or the adherent mucus gel. The muscarinic agonist and the M1 antagonist are thus shown to accelerate the secretion and accumulation, respectively, of mucin in the deep corpus mucosa. Thus intrinsic M1 receptor may possibly be involved in the secretion of mucin in the gastric deep corpus mucosa.

Effects of omeprazole on gastric mucus secretion, tissue prostaglandin synthesis, and acid inhibition in patients with duodenal ulcer: Comparison with ranitidine treatment

Twenty patients with endoscopically diagnosed uncomplicated duodenal ulcer were recruited to study the effects of omeprazole and ranitidine on gastric mucus secretion, duodenal mucosal prostaglandin concentration, and acid output. Ten patients were randomly assigned to therapy with omeprazole 20 mg at bedtime and 10 patients to therapy with ranitidine 300 mg at bedtime for 4 weeks. At entry, before active treatment, gastric juice was collected via a double-lumen gastric probe at 15-minute intervals for 1 hour before and 1 hour after pentagastrin stimulation. Samples of gastric juice were analyzed for both acid content and concentrations of the following components of soluble gastric mucus: protein component, glucosamine, fucose, N-acetyl-neuraminic acid, and sulphate groups. Each patient underwent upper endoscopy with multiple gastric and duodenal biopsies. Prostaglandin E 2 (PGE 2) synthesis was assessed in duodenal specimens. After 4 weeks of treatment, both the gastric probe and endoscopy with biopsies were performed again in all patients. We observed a significant increase in all mucus components and in duodenal PGE 2 content in both treated groups compared with entry values. No treatment differences were detected other than a significant increase in sulfate group levels following treatment with omeprazole ( P = 0.02). Both omeprazole and ranitidine significantly inhibited baseline and pentagastrin-stimulated acid secretion. That inhibition was significantly greater after omeprazole treatment for maximal acid output and peak acid output but not for baseline acid output. We conclude that both omeprazole and ranitidine, when administered at antisecretory doses, increase the concentration of gastric soluble mucus components and stimulate duodenal PGE 2 synthesis. These effects suggest that protective mechanisms are preserved despite a reduction in acid secretion.

Chicken mucin-cross-reactive antigen

We have previously described a chicken heterophile antigenic determinant (CHAD-1) shared by Mycobacterium smegmatis and chicken tissues. We then demonstrated that CHAD-1 is present on several chicken glycoproteins and that its immunoreactive domains are highly branched asparagine-linked oligosaccharides terminating in N-acetylglucosamine residues. In the present study, we have shown that CHAD-1 is also expressed by mucin purified to homogeneity from a soluble mucus of chicken intestine. Another antigen found on chicken mucin is a chicken mucin-cross-reactive antigen (CMCRA). Antisera to this antigen were produced by immunization of rabbits with an enriched preparation of CHAD-1 isolated from the bursa of Fabricius. These antisera were absorbed with Mycobacterium smegmatis (to block the anti-CHAD-1 antibody) and with chicken serum, and then used for immunoperoxidase staining of chicken tissue sections for CMCRA. The latter antigen was detected in most medullary cells of the bursa, in epithelial cells and Hassal's corpuscles of the thymus, and in mucus-producing cells of the intestine, esophagus, trachea, and bronchi. Using Western immunoblot analysis, we demonstrated that CMCRA is expressed by a number of polypeptides extracted from bursal lymphoid cells. These polypeptides could not be detected in extracts of thymus, spleen, peripheral blood or bone marrow mononuclear cells.

Gastric mucosal lesions in streptozotocin-diabetic rats

Formation of gastric mucosal lesions by streptozotocin-induced diabetes was investigated in rats. A single intraveous administration of streptozotocin in a dose of 65 mg/kg effectively produced hyperglycemia and damaged the gastric mucosa. Incidence and severity of mucosal lesions were progressively increased with time, from one to six weeks posttreatment. Microscopic lesions of the mucosa included hyperemia, desquamation of the surface epithelium with diffuse hemorrhage, and severe hemorrhage with localized erosion. Concurrent to the hyperglycemia, the histamine stimulated gastric H +—secretion was significantly decreased whereas pepsin secretion was not affected. Both soluble mucus and surface mucus gel were increased. The result suggests that the early lesion of gastric mucosa may be associated with the direct action of streptozotocin, the severity of which may be further aggravated by diabetic state.

Formation of a fibrin based gelatinous coat over repairing rat gastric epithelium after acute ethanol damage: interaction with adherent mucus.

A gelatinous coat, heterogeneous in appearance, was formed over damaged rat gastric mucosa recovering from acute ethanol injury. This coat, in places 1.6 mm thick (median thickness 680 microns), was 10 times thicker than the translucent layer of adherent mucus (median thickness 70 microns) covering the undamaged mucosa. Immunohistochemistry and periodic acid Schiff staining showed this gelatinous coat to be predominantly a fibrin gel with an exterior layer rich in mucus and necrotic cells. The plasma clotting time was significantly decreased in vitro by pig gastric mucus gel and soluble mucus glycoprotein (90% and 13% respectively) suggesting that in vivo the mucus layer remaining after epithelial damage could act as a template for fibrinogen-fibrin conversion. These results show that a fibrin based gelatinous coat, quite distinct from the adherent mucus layer and with considerable protective potential could be formed over the repairing rat gastric mucosa after acute ethanol damage.

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.