Susumu Ohara

Effects of tetragastrin on mucus glycoprotein in rat gastric mucosal protection

SummaryThe effects of tetragastrin on mucus glycoprotein (mucin) metabolism and mucosal protection in rat gastric mucosa were investigated. Rats were administered with various doses of tetragastrin (12, 120, or 400 [μg/kg body weight; s.c), followed by 50% ethanol-induced gastric injury. Tetragastrin caused a significant increase in mucin content in the corpus mucosa and prevented 50% ethanol-induced gastric mucosal damage in a dose-dependent manner. For assessment of the effects of tetragastrin on the metabolism of gastric mucin in detail, changes in mucin distribution in the three different layers of rat gastric mucosa were examined one hour after single administration of tetragastrin. A significant increase in the mucin content was noted in the mucus gel and surface mucosal layer. Mucin content in the deep mucosa corresponding mainly to the mucus neck cell mucin underwent virtually no change by this treatment. An increase in mucin in the mucus gel and surface mucosa would thus appear due to the administration of tetragastrin and may possibly be related to the protective action of the gastric mucosa against injury. The data demonstrate a possibility that gastrin may have potential for enhancing gastric mucosal protection associated with mucus secretion and/or mucus synthesis on the surface mucosa of rat gastric mucosa.

Comparative study on mucus glycoproteins in rat stomach and duodenum

The density of mucus glycoprotein compared to that of the corpus, antrum and duodenum was; 1.52, 1.49 and 1.57 g/ml respectively. Carbohydrate composition of gastrointestinal mucus glycoprotein consisted of N-acetylgalactosamine, N-acetylglucosamine, galactose, fucose and sialic acid. Ratios of carbohydrate composition among corpus, antral and duodenal mucus glycoproteins differed. The average length of an oligosaccharide was found to be about 12-13, 14 and 10 sugars in the corpus, antrum and duodenum, respectively. In the corpus, the amino acid content was found to have the following quantitative order: Thr greater than Ser greater than Glx = Pro; in the antrum: Thr greater than Ser greater than Glx; and in the duodenum: Thr greater than Ser greater than Pro. Corpus, antral and duodenal mucus glycoproteins have the blood-group A antigen; antral mucus glycoprotein in particular exhibited strong blood-group A activity.

Changes of Rat Gastric Mucus Glycoproteins in Cytoprotection: Influences of Prostaglandin Derivatives

The effects of two synthetic prostaglandin E derivatives on mucus glycoproteins in the stomachs of rats were evaluated. Neither derivative caused change in mucus glycoprotein content in the gastric corpus or antrum, but both increased the biosynthetic activity of mucus glycoproteins in these regions (about 15-30%). Furthermore, the effects of the pretreatment of these derivatives on conserving mucus glycoproteins in ethanol-induced gastric lesions were examined. Treatment with these derivatives 60 min prior to 70% ethanol administration markedly inhibits the decrease in gastric mucus glycoprotein content caused by 70% ethanol. But the glycoprotein content under these pretreatment conditions was significantly less (12-19%) than that in the control group without any drug treatment.

Effects of fasting on mucus glycoprotein in rat stomach

Quantitative changes and chemical composition of gastric mucus glycoproteins in rats after fasting for 24 and 72 hr were studied. The amount of glycoproteins increased in the corpus mucosa during these periods (220% in control for 72 hr), but remained the same in the antrum. The acidity of corpus glycoproteins decreased during the fasting.

Mechanisms for cytoprotection by vitamin U from ethanol-induced gastric mucosal damage in rats

A comparison was made of the effects of a nonsulfhydryl compound, vitamin U (methylme-thioninesulfonium chloride, MMSC), and a sulfhydryl compound, cysteine (Cys), with regard to the inducement of acute gastric mucosal damage in the presence and absence ofN-ethylmaleimide (NEM), a sulfhydryl-blocking reagent. The effects of MMSC, Cys, or NEM on gastric mucin content were examined using a newly developed biochemical method. MMSC and Cys inhibited mucosal damage due to 50% ethanol. The preinjection of NEM had no effect on cytoprotection of prostaglandins, but prevented the effects of Cys and MMSC. MMSC and Cys increased surface mucin content but lessened that of deep mucin. NEM decreased surface mucin and increased deep mucin. It thus follows that sulfhydryl compounds accelerate the secretion of deep mucin and accumulate surface mucin. The cytoprotective mechanism of MMSC may thus be mediated by sulfhydryl compounds, and the increase in surface mucosal mucin may possibly be related to cytoprotection.

Effects of the M1 muscarinic receptor antagonist pirenzepine on gastric mucus glycoprotein in rats with or without ethanol-induced gastric damage.

Changes in gastric mucus glycoprotein (mucin) isolated from pirenzepine-treated rats with or without ethanol (50%)-induced gastric damage were studied. The prior administration of pirenzepine inhibited significantly and dose-dependently the occurrence of macroscopically observable hemorrhagic lesions induced by treatment with ethanol. The gastric mucosa was separated into the surface mucosa, including the mucus gel layer, and the deeper mucosa by mechanical scraping, and the mucin in each was isolated. In ethanol-treated animals the mucin content of the deep corpus mucosa was significantly reduced to 68% the control value. This reduction was inhibited by pretreatment with pirenzepine. In the surface mucosa mucin content was also reduced to 48% of control value by ethanol treatment, but pirenzepine pretreatment increased mucin content to 235% the control value. Total mucin content in the entire stomach essentially resumed the control level by pretreatment with 100 mg/kg of pirenzepine. A single oral administration of pirenzepine (100 mg/kg) caused no change in total mucin content, but mucin in the deep corpus mucosa selectively and significantly increased to 124% the control. These and the results of carbohydrate analysis of purified mucin indicate that pirenzepine administration possibly accelerates the secretion of accumulated deep corpus mucus, retains this deep mucus on surface mucosal mucus, and protects the gastric mucosa in ethanol-induced gastric damage. This may be related to the antiulcerogenic effects of pirenzepine.

A new method of separation and quantitation of mucus glycoprotein in rat gastric mucus gel layer and its application to mucus secretion induced by 16,16-dimethyl PGE2

SummaryA method was established for recovering the mucus gel layer of rat gastric mucosa without damage to underlying surface epithelium. The mucus gel was solubilized by stirring the gastric mucosa in a solution of N-acetylcysteine (NAC), a mucolytic agent. Optimal mucus gel solubilization was possible by treatment with 2% NAC for 5 minutes at room temperature. Mucus glycoprotein was quantitatively extracted and measured from the mucus gel sample obtained by the NAC treatment. This treatment caused no damage to surface epithelial cells, as observed by a light microscope. Besides NAC, pronase solution was also adequate for solubilizing the mucus gel layer without any damage to the surface epithelium. However, extraction and measurement of mucus glycoprotein from the pronase-treated mucus gel sample was not possible due to contamination by high molecular hexose-containing substances which were eluted along with the mucus glycoprotein from the column of Bio-Gel A-1.5m. This NAC method was used to examine changes in mucus glycoprotein content in the mucus gel at one hour following the oral administration of 16,16-dimethyl prostaglandin E2. A significant increase in mucus glycoprotein of the gel was brought about by the prostaglandin treatment. Thus, the present method was suitable for estimating the amount of mucus secreted in to the mucus gel layer.

Efficacy of anti-ulcer drugs on the recovery of gastric mucosal glycoproteins with aspirin-induced gastric damage in rat

SummaryThe efficacy of two anti-ulcer drugs, Cimetidine and Cetraxate, on the mucus glycoproteins of gastric mucosa in the aspirin-induced gastric damage was studied in rats. Simultaneous or previous oral administration of Cimetidine or Cetraxate with aspirin reduced the diminution in the mucus glycoproteins which was occurred by aspirin administration. The recovery of the content of mucus glycoprotein in drug dosed rats occurred within 3 h after aspirin dosing and was nearly 90% of control at 5 h in all cases. Single administration of Cetraxate or Cimetidine produced an increase in the mucus glycoprotein content greater than that of the untreated control. Although a macroscopical method for the measurement of gastric damage was applied to this work, neither erosions nor linear ulcers were observed in all cases except the single administration of aspirin. The biochemical method used should be able to assess the efficacy of drugs on the mucosal lesion which cannot be expressed as the ulcer index.

Compensatory response of colon tissue to dextran sulfate sodium-induced colitis.

Abstract: Depletion of goblet cells (the main mucin-producing cells in the colon) is one of the most reliable histological characteristics of ulcerative colitis, whereas a major symptom of this disease is bloody diarrhea containing a large amount of mucus. The discrepancy between these phenomena was investigated in a time-course study in rats with experimental colitis induced by treatment with oral dextran sulfate sodium (DSS) for 1, 3, or 5 days. Biochemical analysis showed a reduction in mucin content in the distal side of the colon that was proportional to the duration of DSS administration. In the proximal side of the colon, however, there was a significant increase in mucin content already on the first day of treatment with DSS. This increase in colonic mucin content continued for the 5 days of treatment. In the distal side, both sulfomucin and sialomucin decreased proportionally to the duration of DSS administration. In the proximal side, there was an increase in high iron diamine-Alcian blue-positive mucins, and confirming the proliferation of goblet cells. The proliferated glands were predominantly sialylated. Goblet cell depletion and an increase in mucin production occurred in different parts of the colon. This phenomenon may be a type of compensatory function of colon tissue in response to the localized decrease of mucin production in certain portions of the colon.

Distribution of mucosal macromolecular glycoproteins in rat stomach.

1. The mucosal macromolecular glycoproteins were extracted from forestomach, corpus and antrum region of rat whose weight ratio was 2:5:1, respectively. 2. The glycoproteins were fractionated on Bio-Gel A-1.5 m. 96% of the glycoproteins was localized in glandular stomach. 3. The carbohydrate of the glycoproteins composed of N-acetylgalactosamine, N-acetylglucosamine, galactose, fucose and sialic acid in the proportions 1.0:2.7:3.2:1.0:0.14 for corpus, while 1.0:1.4:1.5:0.7:0.04 for antrum.