Gastric Mucosal Defense Research Articles

Fulminant peptic ulcer disease in cardiac surgical patients: pathogenesis, prevention, and management.

To identify pathogenetic factors associated with the development of peptic ulcers in patients following cardiac surgery and to examine the efficacy of medical and surgical therapy of peptic ulcers in this setting. Retrospective study with randomly selected case controls. University hospital referral practice. A total of 9,199 consecutive patients undergoing procedures requiring cardiopulmonary bypass between January 1, 1980 through September 30, 1988, were reviewed. Life-threatening ulcer complications were defined as hemorrhage of greater than 2 units of packed red blood cells which prompted subspecialty consultation and required a therapeutic intervention. Patients who developed life-threatening complications of peptic ulcers (32/9199, 0.35%) (group 1) were compared with 32 randomly selected patients (group 2) for differences in potential pathogenetic factors and outcome. Gastrointestinal hemorrhage, perforated ulcers, death. Patients in group 1 were significantly older than patients in group 2 (66.7 +/- 7.9 vs. 54 +/- 10 yrs, p less than .01). Complications following cardiopulmonary bypass requiring further surgery or causing prolonged hypotension were significantly more frequent in patients with ulcers than in controls (10/32 vs. 1/32, p less than .005). The mortality rate for patients in group 1 was 34.3% (11/32) compared with 0% in group 2 (p less than .001). Perioperative ulcer prophylaxis was employed with equal frequency in groups 1 and 2 and did not correlate with outcome. The development of complications of postoperative peptic ulcers following cardiac surgery correlates with age, need for reoperation, and hypoperfusion, but not with the use of prophylactic regimens to suppress acid secretion. These results suggest that impairment of gastric and duodenal mucosal defense mechanisms is a critical factor in the development of postoperative peptic ulcers.

Taurocholate induced gastric mucosal injuries in experimental portal hypertension.

The susceptibility of the gastric mucosa to injury by topical sodium taurocholate (40 mmol/l) in hydrochloric acid (150 mmol/l) was studied in prehepatic and cirrhotic rat models of portal hypertension. Portal venous pressure was increased in rats who had undergone partial portal vein ligation compared with rats that had undergone sham operation on days 3, 7, and 28 after operation (20.6 (0.9), 14.8 (0.8), and 11.3 (0.5) mm Hg v 7.3 (0.7), 7.3 (0.6), and 8.2 (0.2) mmHg respectively (mean (SEM)). At day 3 gastric mucosal injuries were increased in rats with partial portal vein ligation compared with sham operated rats (55.3 (9.4) vs 22.3 (10.5) mm2, p = 0.006), but at the later time intervals there was no significant difference in injuries between the two groups. In rats with carbon tetrachloride induced hepatic cirrhosis, portal pressure was increased (15.6 (1.0) v 6.7 (0.6) mmHg), but again there was no significant difference in mucosal injuries relative to control animals. We conclude that gastric mucosal defence mechanisms are impaired in acute but not chronic experimental portal hypertension.

Effects of FRG-8813, a new-type histamine H2-receptor antagonist, on the healing of gastric and duodenal ulcer in rats and spontaneously ulcerative mice

We examined the anti-ulcer effects of FRG-8813, a new-type histamine H2-receptor antagonist, in chronic ulcer models of rats and mice (W/WV). FRG-8813, given orally twice a day for 7 days, accelerated the healing of gastric or duodenal ulcer induced by acetic acid injection or application at the non-antisecretory doses (0.3 approximately 3 mg/kg). Administration of FRG-8813 to rats with ulcers increased the amounts of mucus in the gastric mucosa. These actions of FRG-8813 were more potent than those of famotidine or cimetidine. In W/WV mice, several ulcers spontaneously developed on gastric mucosa during the 8 weeks after the birth. The ulcers were aggravated by several unknown factors after the ulcer generation in W/WV mice. The aggravation of ulcers was inhibited by the 4-week administration of FRG-8813 with diet at the dose of 1 or 10 mg/kg/day, but was not inhibited by cimetidine at the dose of 100 mg/kg/day. From these results, we suggest that FRG-8813 is able to accelerate the healing of ulcers by antisecretory plus increasing actions on the integrity of the gastric mucosal defense mechanisms; therefore FRG-8813 is expected to be a useful drug for the treatment of gastric or duodenal ulcers in humans.

Mechanisms of Gastric Mucosal Injury and Protection

This article emphasizes and reviews the premise that because the pathogenesis of acute gastric mucosal injury is multifactorial, several protective mechanisms should also be considered in analyzing gastric mucosal defense. The first part of the article reviews the pathogenesis of acute gastric mucosal injury by major etiologic factors such as hypoxia and chemical and biological agents, and emphasizes the common endogenous mediators of damage (e.g, endothelins, leukotrienes, thromboxane, platelet-activating factor, monoamines, free radicals, proteases, ammonia, hydrochloric acid, and bile acids--in decreasing potency). The second part of the review is devoted to the gastroprotective mechanisms that are analyzed by anatomical (histologic) location and biochemical processes. The endogenous mediators of acute gastroprotection include prostaglandins, sulfhydryl (SH) compounds, non-SH antioxidants, polyamines, and epidermal growth factor, whereas the protective and mediatory role of glucocorticoids, somatostatin, pentagastrin, histamine, gangliosides, and calcitonin gene-related peptide need further studies. A list of endogenous and exogenous chemicals that exert biphasic, damaging, and protective effects on the gastric mucosa in also included. The final common pathway of acute gastroprotection at the structural and functional level seems to be the preservation of subepithelial microvascular integrity leading to maintenance of mucosal blood flow that allows the energy-dependent rapid restitution (cell migration) from surviving gastric neck cells to repair the superficial epithelial defect. Very new data on the contribution of a histodilutional barrier and release of proteases to gastroprotective processes are also discussed.

Inability of cytoprotection to occur during a period of gastric ischemia

Prostaglandin E2 (PGE2), colloidal bismuth subcitrate (CBS), and sucralfate (SUC) are known to protect the gastric mucosa from ethanol injury. The proposed central role for the microcirculation in gastric mucosal defense and as a site for the expression of the protective effects of these agents was investigated in the rat stomach. Animals were pretreated with either PGE2, CBS, or SUC. Control rats were given normal saline. After allowing 15 min for expression of the pretreatment, ethanol was administered as a 10%, 25%, 50%, or 100% solution to groups of rats with normally perfused stomach and to other groups of rats in whom the stomach was made ischemic by cross-clamping the supracoeliac aorta immediately prior to the instillation of ethanol. The extent of gastric mucosal damage was measured using quantitative histological techniques and expressed as a percentage of surface area and volume of mucosa damaged. In the presence of ischemia, the extent of damage by ethanol was markedly increased, with total destruction of the mucosa by the 50% and 100% solutions. With 25% ethanol, the volume of mucosal damage was increased from 0.5% in the normally perfused stomach to 53.5% with ischemia. When 10% ethanol was instilled into the ischemic stomach, only 0.8% of the volume of the mucosa was damaged, which was not different from the volume of mucosa damaged after the ischemic stomach was exposed to normal saline alone (1.0%). Pretreatment with PGE2, CBS, or SUC did not significantly change the extent of damage seen with exposure of the ischemic stomach to 25% or 50% ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Peptidergic Sensory Neurons in Gastric Mucosal Blood Flow and Protectiona

The present findings have revealed a new aspect of how mechanisms of gastric mucosal resistance to injury are called into effect and are coordinated by the nervous system. Capsaicin-sensitive sensory neurons in the stomach play a physiological role in monitoring acid influx into the superficial mucosa. Once activated, they strengthen gastric mucosal defense against deep injury, with a key process in this respect being an increase in blood flow through the gastric mucosa. This concept opens up completely new perspectives in the physiology and pathophysiology of the gastric mucosa if we consider that the long-term integrity of the gastric mucosa may be under the subtle control of acid-sensitive sensory neurons and that, vice versa, improper functioning of these neutral control mechanisms may predispose to gastric ulcer disease. The present observations also indicate that some of the peptides contained in gastric sensory nerve endings might fulfill a transmitter or mediator role in controlling gastric mucosal blood flow and integrity. Whereas substance P and neurokinin A are unlikely to play a role in the regulation of gastric mucosal blood flow, there is severalfold evidence that CGRP is very important in this respect. This peptide, which in the rat gastric mucosa originates exclusively from spinal sensory neurons, is released upon stimulation of sensory nerve endings and is extremely potent in facilitating gastric mucosal blood flow and in protecting the mucosa from injurious factors. Selective ablation of spinal sensory neurons containing CGRP weakens the resistance of the gastric mucosa against acid injury, which is most likely due to inhibition of protective vasodilator reflexes. We now aim at providing direct pharmacological evidence that antagonism of endogenously released CGRP results in similar pathophysiological consequences as ablation of capsaicin-sensitive sensory neurons.

Sucrose octasulfate stimulates gastric somatostatin release

To explore the mechanisms of the effects of sucralfate on the stomach, we investigated the action of sucrose octasulfate (SOS), a constituent of sucralfate, on the function of canine gastric parietal cells and somatostatin cells and in the isolated perfused intact rat stomach. Somatostatin cells from the canine gastric fundus were isolated by EDTA-collagenase dispersion and counterflow elutriation, and somatostatin-like immunoreactivity (SLI) release in response to SOS was measured by radioimmunoassay. Similar methods were used to isolate gastric parietal cells, in which gastric acid secretion was measured by uptake of a radiolabeled weak base, [ 14C]aminopyrine. SLI release by the intact rat stomach was examined in an isolated vascularly perfused rat stomach model. SOS, either alone or co-administered with epinephrine or gastrin heptadecapeptide (G17), dose-dependently stimulated SLI release by isolated canine fundic D-cells. At the highest doses, SOS potentiated the effect of epinephrine but not G17. Similarly, SOS potentiated the stimulating effect of dibutyryl cyclic adenosine 3′,5′-monophosphate (DBcAMP), but not 12- O-tetradecanoylphorbol 13-acetate (TPA). The effect of SOS on SLI release could be inhibited by octreotide, a somatostatin analogue. SOS did not alter acid secretion by cultured canine parietal cells either in the basal state or when coadministered with acid secretagogues. In isolated perfused rat stomach studies, SOS produced a significant (60% greater than basal) increase in SLI secretion. There was a similar effect when SOS was perfused against a background of isoproterenol. SOS stimulates SLI release from gastric somatostatin cells and from the isolated perfused stomach but has no direct effect on gastric parietal cells. These actions of SOS may mediate in part the apparent ability of sucralfate to enhance gastric mucosal defense.

The role of calcitonin gene‐related peptide in gastric mucosal protection in the rat

The presence of circulating antibodies to calcitonin gene-related peptide (CGRP) enhanced the damaging effect of ethanol on the rat gastric mucosa. Taken together with previous experimental and morphological data the results suggest that CGRP released from the peripheral terminals of visceral afferent fibres plays a role in mediating gastric mucosal defence mechanisms.

Studies on the Mechanism for the Gastric Mucosal Protection by Famotidine in Rats

The effect of famotidine on gastric lesions induced by the decrease in mucosal defensive resistance was investigated in rats and compared with those of cimetidine, pirenzepine and cetraxate. Famotidine (0.03, 0.1 and 0.3 mg/kg. p.o.) inhibited dose-dependently the development of gastric lesions produced by taurocholatehistamine in doses that suppressed histamine-induced acid secretion in pylorus-ligated rats. The H2-antagonist also prevented gastric mucosal lesions induced by taurocholate-serotonin, iodoacetamide, acidified aspirin and acidified ethanol. Cimetidine, pirenzepine and cetraxate showed the inhibitory effects on almost all types of the gastric lesions, but their inhibitory effects were much less potent than those of famotidine. On the other hand, famotidine inhibited the decreases of gastric mucosal blood flow induced by acidified ethanol and the mucosal contents of glycoprotein induced by water immersion restraint stress. In addition, famotidine increased the transgastric potential difference (PD) and promoted the recovery of decreased transgastric PD induced by acidified ethanol in rats. These results suggest that the preventive effect of famotidine on gastric lesions is attributable not only to suppression of acid secretion but to activation of the gastric mucosal defensive mechanisms.

Studies on the mechanism for the gastric mucosal protection by famotidine in rats.

The effect of famotidine on gastric lesions induced by the decrease in mucosal defensive resistance was investigated in rats and compared with those of cimetidine, pirenzepine and cetraxate. Famotidine (0.03, 0.1 and 0.3 mg/kg, p.o.) inhibited dose-dependently the development of gastric lesions produced by taurocholate-histamine in doses that suppressed histamine-induced acid secretion in pylorus-ligated rats. The H2-antagonist also prevented gastric mucosal lesions induced by taurocholate-serotonin, iodoacetamide, acidified aspirin and acidified ethanol. Cimetidine, pirenzepine and cetraxate showed the inhibitory effects on almost all types of the gastric lesions, but their inhibitory effects were much less potent than those of famotidine. On the other hand, famotidine inhibited the decreases of gastric mucosal blood flow induced by acidified ethanol and the mucosal contents of glycoprotein induced by water immersion restraint stress. In addition, famotidine increased the transgastric potential difference (PD) and promoted the recovery of decreased transgastric PD induced by acidified ethanol in rats. These results suggest that the preventive effect of famotidine on gastric lesions is attributable not only to suppression of acid secretion but to activation of the gastric mucosal defensive mechanisms.

Effects of the New Anti-Ulcer Agent KB-5492 on Experimental Gastric Mucosal Lesions and Gastric Mucosal Defensive Factors, as Compared to Those of Teprenone and Cimetidine

Effects of the New Anti-Ulcer Agent KB-5492 on Experimental Gastric Mucosal Lesions and Gastric Mucosal Defensive Factors, as Compared to Those of Teprenone and Cimetidine

Failure of prostacyclin, β-carotene, atropine and cimetidine to produce gastric cyto- and general mucosal protection in surgically vagotomized rats

Different chemicals (such as ethanol, HCl, drugs) produce gastric mucosal injury. A special type of gastric mucosal defense, which differed from the inhibition of gastric acid secretion, was discovered in response to small doses of prostaglandins. This phenomenon was termed “gastric cytoprotection”. Later, the existence of gastric cytoprotection was proved using different compounds, such as vitamin A and other carotenoids, prostacyclin, small doses of anticholinergic and H 2-blocking agents. These compounds produce cytoprotection by different mechanims. In this study we tested the role of vagus nerve on the development of these different types of gastric cytoprotection. These compounds prevent ethanol-induced gastric mucusal injury in rats with intact vagus nerve, but their cyto- and mucosal protective effects disappear in surgically vagotomized rats. These results indicate that the intact vagus nerve is basically necessary for the overproduction of HCl and pepsin secretion, and for the development of gastric cytoprotection, produced by different compounds (e.g. prostacyclin, β-carotene, small doses of atropine and cimetidine) acting without the presence of inhibition of gastric acid secretion.

Effects of the New Anti-Ulcer Agent KB-5492 on Experimental Gastric Mucosal Lesions and Gastric Mucosal Defensive Factors, as Compared to Those of Teprenone and Cimetidine.

Effects of KB-5492, a new anti-ulcer agent, on various experimental gastric mucosal lesions and mucosal defensive factors in rats were compared with those of teprenone and cimetidine. KB-5492 administered orally at 12.5-200 mg/kg inhibited water-immersion stress- and indomethacin-induced gastric mucosal lesions in a dose-dependent manner with ED50 values of 46 and 27 mg/kg, respectively, indicating that KB-5492 was more potent than teprenone but less potent than cimetidine. KB-5492, administered orally at 12.5-100 mg/kg, also inhibited ethanol-induced gastric mucosal lesions in a dose-dependent manner with an ED50 of 23 mg/kg, so KB-5492 was 3 times more potent than teprenone, whereas cimetidine produced no obvious inhibition. In addition, KB-5492, administered orally at 25 and 50 mg/kg twice daily for 10 consecutive days, significantly accelerated the healing of acetic acid-induced gastric ulcers more potently than teprenone and cimetidine. KB-5492 at anti-ulcer doses significantly increased gastric mucosal blood flow in normal anesthetized rats and inhibited the reduction of gastric mucosal hexosamine content induced by aspirin, but did not affect gastric acid secretion in pylorus-ligated rats. These results indicate that KB-5492 has potent and broad anti-ulcer properties, which are probably exerted by its enhancement of gastric mucosal defensive factors through increasing gastric mucosal blood flow and/or retaining gastric mucus, and not by its inhibition of gastric acid secretion.

Effects of 12-Sulfodehydroabietic Acid Monosodium Salt (TA-2711), a New Anti-Ulcer Agent, on Gastric Mucosal Lesions Induced by Necrotizing Agents and Gastric Mucosal Defensive Factors in Rats

AbstractEffects of TA-2711 on gastric mucosal lesions induced by various necrotizing agents and several defensive factors of gastric mucosa were investigated in rats. Oral administration of TA-2711 at 12.5 to 200 mg/kg prevented the formation of gastric mucosal lesions induced by 99.5% ethanol, 0.6 N HCl, 0.2 N NaOH and boiling water with ED50 values of 24, 58,16 and 101 mg/kg, respectively. Oral TA-2711 at 100 mg/kg increased the gastric mucosal prostaglandin E2 (PGE2) level without any change in transmucosal potential difference. A sustained decrease in gastric mucosal blood flow produced by intragastric administration of 99.5% ethanol was inhibited by oral TA-2711 (50,100 mg/kg) and 16, 16-dimethyl PGE2 (10 μg/kg). The effect of TA-2711 on ethanol-induced decrease in blood flow was suppressed by Indomethacin (10 mg/kg, s.c). Oral TA-2711 (25–100 mg/kg) dose-dependently increased the amount of mucus adherent to the gastric mucosa. In addition, gastric HCO3- secretion was increased by intragastric TA-2711 at 2.5 and 5.0 mg/ml. These results suggest that TA-2711 enhances gastric mucosal resistance by increasing mucus and HCO3- secretion and by maintaining mucosal blood flow, and protects the gastric mucosa against various irritants. The effects of TA-2711 appear to be mediated by mucosal prostaglandins such as PGE2.

Intragastric capsaicin protects against aspirin-induced lesion formation and bleeding in the rat gastric mucosa

Previous work has indicated that capsaicin-sensitive afferent neurons are involved in gastric mucosal defense mechanisms. The present study investigated whether stimulation of these neurons by intragastric administration of capsaicin would protect against aspirin-induced mucosal damage in the luminally perfused rat stomach. Capsaicin (25–640 μM), administered together with acidified (pH 1.5) aspirin (25 mM), inhibited macroscopically visible lesion formation and gastric bleeding in a concentration-dependent fashion. Capsaicin (160 μM) also attenuated the aspirin-induced fall in the gastric potential difference. An inhibitory effect of capsaicin (160 μM) on aspirin-induced gastric injury was also seen by light and scanning electron microscopy. Aspirin alone caused a vast ablation of the gastric surface epithelium, resulting in exposure of the lamina propria. In the presence of capsaicin, the depth of mucosal injury, the area totally deprived of surface epithelial cells, and the severity of surface desquamation were diminished. As capsaicin is a selective stimulant of thin afferent neurons, it would appear that these neurons participate in mechanisms of gastric defense against aspirin injury. Prevention of hemorrhagic damage seems to be the primary effect of afferent nerve-mediated gastroprotection, although injury to the surface epithelium is also reduced to some degree.

Augmentation of the gastric mucosal defense mechanism induced by KW-5805, a novel antiulcer agent.

KW-5805 (a new antiulcer agent), given p. o. at 30 mg/kg to rats, significantly increased the amount of gastric adherent mucus and mucosal glycoproteins. Gastric mucosal glucosamine synthetase activity was significantly enhanced by KW-5805 (30 mg/kg, p. o.). KW-5805 (10, 30 mg/kg, p. o.) significantly suppressed the decrease of gastric mucosal blood volume and oxygen sufficiency induced by hemorrhagic shock. The agent also significantly inhibited the extravasation of Evans blue into the gastric mucosa after ischemia-reinfusion. In conclusion, KW-5805 increased biosynthesis, storage and secretion of gastric mucus and improved the gastric mucosal hemodynamics.

Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach

the role that nitric oxide, an endothelium-derived relaxing factor, may play in the regulation of gastric mucosal defence was investigated by assessing the potential protective actions of this factor against the damage caused by ethanol in an ex vivo chamber preparation of the rat stomach. Topical application of glyceryl trinitrate and sodium nitroprusside, which have been shown to release nitric oxide, markedly reduced the area af 70% ethanol-induced hemorrhagic damage. Topical application of a 0.01% solution of authentic nitric oxide also significantly reduced the severity of mucosal damage. Pretreatment with indomethacin precluded the involvement of endogenous prostaglandins in the protective effects of these agents. The protective effects of NO were transient, since a delay of 5 minutes between NO administration and ethanol administration resulted in a complete loss of the protective activity. The protection against ethanol afforded by 10 mug/ml nitroprusside could be completely reversed by intravenous infusion of either 1% methylene blue or 1 mM hemoglobin, both of which inhibit vasodilation induced by nitric oxide. Intravenous infusion of 1% methylene blue significantly increased the susceptibility of the mucosa to damage induced by topical 20% ethanol. These results indicate that ethanol-induced gastric damage can be significantly reduced by nitric oxide. The mechanisms underlying the protective actions of nitric oxide are unclear, but may be related to its vasodilator or anti-aggregatory properties.

Gastric mucosal protection and superoxide dismutase.

Diethyldithiocarbamate (DDC), an inhibitor of Cu,Zn-superoxide dismutase (SOD), at a dose of 500 mg/kg or aminotriazole (AT), an inhibitor of catalase, at a dose of 2,000 mg/kg reduced slightly gastric mucosal SOD activity, did not change gastric mucosal blood flow (GMBF), and did not cause gastric ulcers. However, when both DDC and AT were administered together, gastric mucosal SOD activity and GMBF remarkably decreased, and gastric ulcers appeared. Moreover, the administration of SOD attenuated gastric ulcer induced by DDC plus AT. These results suggested that SOD may play an important role in the gastric mucosal defense mechanisms against active oxygen species.

Involvement of autonomic nervous system in gastric mucosal defense mechanism.

This article describes the histochemical, immunohistochemical, radioautographic, and ultrastructural localizations of aminergic and peptidergic nerves, neurotransmitter receptors, and their binding sites in the stomach wall. Cholinergic and vasoactive intestinal polypeptide (VIP)-ergic nerve fibers are distributed along the gastric microvasculature, within the myenteric and submucosal plexuses, and in the muscularis mucosae and circular muscle layer. In the mucosa, both nerve fibers evenly extend along the capillaries in association with the epithelial cells up to the mucosal surface. In particular, cholinergic nerves are proved to doubly innervate the mucosal capillaries and nonmuscular venules as well as the parietal cells. Adrenergic and neuropeptide Y (NPY)-containing nerves are distributed primarily along the arterioles of the gastric microvasculature, within the myenteric plexuses, and in the circular muscle layer. These nerve fibers extend up to the basal portion of the mucosa in close association with small arterioles, capillaries, and epithelial cells. Some of the adrenergic nerve axons are coexistent with the cholinergic nerve axons within the Schwann cell. Histamine H1 receptors are widely located on the walls of arterioles, capillaries and venules, while H2 receptors are evident not only on the parietal cells but also on the walls of the collecting venules and surrounding capillaries in the mucosa. Dopamine D1 receptors are predominantly located on the smooth muscle cells of the arterioles near the muscularis mucosae, while D2 receptors are present on the walls of postcapillary venules and collecting venules. Functional coordination of both intramural peptidergic nerves as intrinsic origin and aminergic nerves as extrinsic origin is considered to be essential for maintaining the gastric mucosal defense mechanism against a variety of aggressive factors.

Prostaglandin effect on the enzymatic sulfation of mucus glycoprotein in gastric mucosa

The effect of 16,16-dimethyl prostaglandin E 2 (DMPGE 2 on the sulfation of mucus glycoprotein in gastric mucosa was investigated. The enzymatic activity which catalyzes the transfer of the sulfate ester group from 3'-phosphoadenosine-5'-phosphosulfate to gastric mucus glycoprotein was located in the detergent extracts of Golgi-rich membrane fraction of antral and body mucosa of rat stomach. The sulfotransferase activity of this fraction from body mucosa, however, was 35% higher than that from the antrum. The enzyme exhibited optimum activity at pH 6.8 using 0.5% Triton X-100 and 30 mM NaF. The apparent K m of the enzyme for sulfation of mucus glycoprotein was 10.5 μM, and the sulfate ester was found incorporated into the carbohydrate chains of the glycoprotein. Introduction of DMPGE 2 to the reaction mixtures led to an enhancement in the rate of mucus glycoprotein sulfation. The rate of enhancement was proportional to the concentration of DMPGE 2 up to 1.0 × 10 −4 M and was of the competitive type, with an apparent K m value of 6.7 μM. Since sulfated mucins play an important role in gastric mucosal defense and the increase in their sulfation occurred at levels of prostaglandin present in gastric mucosa, the observed effect may be of significance to gastric mucosal defense in vivo.