Effects of Fasting, Stress and Drugs on Gastric Glycoprotein Synthesis in the Rat

Abstract

1The relationship between gastric mucosal damage and synthesis of gastric glycoproteins, as measured by the rate of incorporation of N-acetyl-[3 H]glucosamine, was investigated in rats after fasting and restraint stress and a single administration of aspirin (200 mg/kg, orally), phenylbutazone (200 mg/kg, orally), prednisolone (200 mg/kg, orally), or adrenaline (2 mg/kg, i.p.). In one experiment, the effects of aspirin and phenylbutazone on carbohydrate content of the glycoproteins were also determined. 2 Restraint stress, phenylbutazone and aspirin resulted in acute gastric mucosal erosions in some of the rats. Adrenaline produced severe sub-mucosal haemorrhage, but no erosions or ulceration, while prednisolone and fasting gave no gross pathology. 3 The rate of incorporation of N-acetyl-[3 H]glucosamine into glycoproteins was decreased after all treatments except adrenaline. In the groups receiving restraint stress, aspirin or phenylbutazone, the decreases were more marked in rats which developed erosions than in those with no gastric pathology. 4 Aspirin and phenylbutazone also produced changes in the carbohydrate content of the glycoproteins, the effects again being greater in the rats which developed erosions. 5 The results are discussed in the context of a possible association between erosion formation and glycoprotein synthesis and it is proposed that inhibition of mucus glycoprotein biosynthesis may be one mode of action of stress and drugs in causing gastric mucosal damage.

Effect of an anti-ulcer agent, 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy) chalcone (SU-88), on the biosynthesis of gastric sulfated mucosubstances in restrained and water-immersed rats.

“…A similar relationship between ulcerogenesis and the reduction in the synthesis of gastric mucosub stances has been reported by other investi gators (9-11, 14, 15). Dekanski et al (9) have shown that the impaired glycoprotein synthesis was a causative biochemical phenomenon prior to the development of gastric mucosal damage rather than a mere result of it.…”

“…On the other hand, it is well-known that gastric mucosubstances also play an im portant role in the defense against ulceration (6)(7)(8)(9)(10)(11).…”

A wider view on gastric erosion: detailed evaluation of complex somatic and behavioral changes in rats treated with indomethacin at gastric ulcerogenic dose

“…Gastric mucosa of fasted animal is more susceptible to ulcerogenic stimuli for several, local reasons, including an absence of protective role of chimus and deficiency of glycoproteins in mucus (Dekanski et al 1975). On the other hand, fasting may induce general changes in the body, which makes it more vulnerable to ulcerogenic stimuli.…”

Changes in the Incorporating Activity of 35S-Sulfate into Gastric Sulfated Glycoproteins in the Rat with Erosions by Restraint and Water Immersion Stress

“…Discussion It is well known that the gastric surface mucosal cells produce a large amount of glycoproteins with the concomitant death of the cells, and these gastric glycoproteins including sulfated glycoproteins (SGP) are important in protecting the underlying mucosa from peptic digestion. There are many reports about the relationship between gastric mucosal damage and the synthesis of gastric glycoproteins (1)(2)(3)(4)(5)(6). It has been demonstrated that the mucosal SGP had apparent peptic inhibitory activity due to the binding of SGP to the protein substrate for pepsin and protected the gastric mucosa!…”

“…It has been reported by many investigators that erosions and hemorrhages of the gastric mucosa produced by anti-inflammatory drugs or stress load were associated with impaired mucus production, and the alterations in the production of mucus may account for the decrease in its protective capacity (1)(2)(3)(4)(5)(6). It is thought that the increased biosynthesis of gastric glycoproteins and glycosaminoglycans may be predominant factors in the protection and healing of gastric ulcers (7).…”