N-ethylmaleimide antagonizes stress-induced gastric ulcers in rats

Summary N-ethylmaleimide (NEM) 10 or 25 mg/kg b.wt, given s.c. 20 min beforehand, dose-dependently and significantly antagonizes the severity of gastric glandular ulcers produced by restraint at 4°C (stress) for 2 h. These findings suggest that reduced activity of endogenous nonprotein sulfhydryl substances in gastric tissue does not worsen stress-induced ulceration in rat stomachs, unlike the deleterious effect its depletion is claimed to have on ethanol-evoked gastric mucosal damage. Thus, decreased SH activity appears not to play a role in the aetiology of mucosal ulcers due to stress.     

The influence of peripheral or central administration of ondansetron on stress-induced gastric ulceration in rats

Ondansetron (0.08, 0.15 or 0.3 mg/kg) injected s.c., every 12h with the fourth dose given 0.5 h before experiments, dose-dependently lessened gastric glandular mucosal ulceration produced by cold-restraint stress for 2h. When given intracerebrally (i.c.) (0.1, 0.5 or 1g), using the same treatment regimen, infusion of ondansetron 1 g into the nucleus amygdaloideus centralis decreased stress-evoked ulcers; in contrast, injection of the same dose into the nucleus accumbens intensified these lesions. The associated stress-induced stomach wall mast cell degranulation was unaffected by all s.c. or i.c. doses of ondansetron. Pretreatment with disodium cromoglycate i.p. alone, or concurrently with ondansetron s.c., prevented not only ulceration but also mast cell degranulation. 5-Hydroxytryptamine₃ receptor antagonism appears to inhibit stress-evoked ulcers mainly by blocking the peripheral effects of the amine after its release from the gastric mucosal mast cells.     

A comparative study of the gastric ulcerogenic effects of stress and reserpine in rats with decreased stomach wall mast cell populations

Summary Stress-induced gastric glandular ulcers in rats appeared less severe than those evoked by reserpine, although glandular mucosal mast cell counts were equally decreased. Prior depletion of the glandular mucosal mast cell population confirmed the hypothesis that an additional mechanism contributes to reserpine ulceration.     

Effect of subdiaphragmatic vagotomy on production of gastric ulcers in pylorus-ligated albino rats.

A reduction in volume and free and total acidity of gastric content was noted along with reduction in ulcer index, with a shift of the site of ulceration from fundus to the glandular part of the stomach, following vagotomy in pylorus-ligated rats. Low volume and acidity explains the absence of ulcers in the fundus, but the increased involvement of glandular part in ulceration is possibly due to weakening of the mucosal barrier following vagotomy.     

Effect of subdiaphragmatic vagotomy on production of gastric ulcers in pylorus-ligated albino rats

Summary A reduction in volume and free and total acidity of gastric content was noted along with reduction in ulcer index, with a shift of the site of ulceration from fundus to the glandular part of stomach, following vagotomy in pylorus-ligated rats. Low volume and acidity explains the absence of ulcers in the fundus, but the increased involvement of glandular part in ulceration is possibly due to weakening of the mucosal barrier following vagotomy.     

Nitric oxide inhibition intensifies cold-restraint induced gastric ulcers in rats

Treatment 20 min beforehand with an inhibitor of nitric oxide (NO) synthesis, N^W-nitro-l-arginine methyl ester (L-NAME) (12.5, 25, 50 or 100 mg/kg, s.c.), dose-dependently intensified gastric glandular mucosal ulceration produced by cold-restraint stress. Hexamethonium (20 mg/kg) or atropine (1 mg/kg) pretreatment s.c. 20 min before stress strongly antagonised stress-evoked ulceration, as well as the ulcer-potentiating effects of L-NAME when either cholinoceptor antagonist was given concurrently with the NO inhibitor. Stress-induced mast cell degranulation was not worsened by L-NAME pretreatment. The findings suggest that NO could confer partial protection against stress-induced gastric ulcer formation; its activity is triggered off by the ulcerogenic mechanism of stress.     

Histamine H1- and H2-receptor-mediated gastric microcirculatory effects in the aetiology of stress ulceration in the rat stomach

Summary Stress produced severe mucosal ulcers, increased mucosal microcirculation and lowered mast cell counts in the glandular wall of rat stomachs. Mepyramine i.m. or metiamide i.p. effectively prevented both ulceration and microcirculatory changes but not stress-reduced mast cell counts.Acknowledgment. The authors thank Dr W.A.M. Duncan (Smith, Kline and French Labs Ltd, England) for the generous gift of metiamide.     

Histamine H1- and H2-receptor-mediated gastric microcirculatory effects in the aetiology of stress ulceration in the rat stomach

Stress produced severe mucosal ulcers, increased mucosal microcirculation and lowered mast cell counts in the glandular wall of rat stomachs. Mepyramine i.m. or metiamide i.p. effectively prevented both ulceration and microcirculatory changes but not stress-reduced mast cell counts.     

Nicotine and ascorbic acid effects on cold-restraint ulcers in rats

Summary Rats were orally administered 1-ascorbic acid, nicotine, 1-ascorbic acid and nicotine, or distilled water for 10 days. Following this treatment they were fasted for 24 h and then restrained in a cold environment for 2h. Nicotine alone produced significantly more gastric ulcers than any other treatment. 1-Ascorbic acid increased ulceration relative to controls. The combined effects of 1-ascorbic acid and nicotine resulted in reduced ulcer incidence and severity. It appears that 1-ascorbic acid and nicotine do not act synergistically to augment stress-induced gastric ulcer. Supported by Natural Sciences and Engineering Research Council of Canada grant No. A 6312.     

Effect of pylorus ligation on gastric mucosal mast cell population in normal and adrenalectomised albino rats

Summary Pylorus ligation in normal albino rats acts like a stressor leading to degranulation of mast cells in gastric mucosa, thereby decreasing their number. This decrease is less pronounced when pylorus ligation is done in adrenalectomized rats. This implies that action of a stressor on gastric function involves the adrenal steroids which liberate the powerful gastric stimulant histamine from gastric mucosal mast cells.     

Effect of pylorus ligation on gastric mucosal mast cell population in normal and adrenalectomised albino rats.

Pylorus ligation in normal albino rats acts like a stressor leading to degranulation of mast cells in gastric mucosa, thereby decreasing their number. This decrease is less pronounced when pylorus ligation is done in adrenalectomized rats. This implies that action of a stressor on gastric function involves the adrenal steroids which liberate the powerful gastric stimulant histamine from gastric mucosal mast cells.     

Gastrin: obligatory intermediate in the postprandial mobilization of gastric histamine in the rat.

In unoperated fasted rats, feeding raised the serum gastrin concentration, reduced the gastric mucosal histamine content and activated the gastric histidine decarboxylase. The reduction of gastric histamine and activation of histidine decarboxylase was induced also by the injection of pentagastrin. In antrectomized rats, feeding failed to produce these effects. Injection of pentagastrin, however, still lowered gastric histamine and activated gastric histidine decarboxylase. Thus, antral gastrin seems to be an obligatory mediator of the postprandial activation of histidine decarboxylase and mobilization of histamine.     

Gastrin: Obligatory intermediate in the postprandial mobilization of gastric histamine in the rat

Summary In unoperated fasted rats, feeding raised the serum gastrin concentration, reduced the gastric mucosal histamine content and activated the gastric histidine decarboxylase. The reduction of gastric histamine and activation of histidine decarboxylase was induced also by the injection of pentagastrin. In antrectomized rats, feeding failed to produce these effects. Injection of pentagastrin, however, still lowered gastric histamine and activated gastric histidine decarboxylase. Thus, antral gastrin seems to be an obligatory mediator of the postprandial activation of histidine decarboxylase and mobilization of histamine.Acknowledgments. Grant support from the Swedish and Danish Medical Research Councils (14P-4822, 04X-1007, 17X-4144 and 512-2540).     

Gastric irrigation and secretion in the ligatured or fistuled pylorus rat upon influence of intra-duodenal olive oil (author's transl)]

Pylorus ligature hides the inhibitory effects of endogenous cholecystokinine-pancreozyme (CCK-PZ) on gastric mucosal secretion and irrigation, whereas the juice collected through transduodenal pyloric fistula makes this phenomenon obvious. It appears that the pyloric fistula encourages inhibition of gastrinic secretion, so that the CCK-PZ can achieve its effects.     

Irrigation et sécrétion gastriques après ligature ou fistule pyloriques chez le rat,sous l'influence d'huile d'olive intra-duodénale

Summary Pylorus ligature hides the inhibitory effects of endogenous cholecystokinine-pancreozyme (CCK-PZ) on gastric mucosal secretion and irrigation, whereas the juice collected through transduodenal pyloric fistula makes this phenomenon obvious. It appears that the pyloric fistula encourages inhibition of gastrinic secretion, so that the CCK-PZ can achieve its effects.     

Sequential ultrastructural study of mucosal innervation following parietal cell vagotomy and antrectomy

Rats having undergone parietal cell vagotomy (PCV) or PCV with antrectomy were sacrificed and gastric mucosal samples studies by electron microscopy. Degeneration of axons was followed by the appearance of small, neurotubule-rich axons which increased in size and number with increasing postoperative interval. The source of these regenerating fibers is unknown but may have come from the fundus.     

Sequential ultrastructural study of mucosal innervation following parietal cell vagotomy and antrectomy

Summary Rats having undergone parietal cell vagotomy (PCV) or PCV with antrectomy were sacrificed and gastric mucosal samples studies by electron microscopy. Degeneration of axons was followed by the appearance of small, neurotubule-rich axons which increased in size and number with increasing postoperative interval. The source of these regenerating fibers is unknown but may have come from the fundus.     

Gastric mucus effusion elicited by oral copper compounds: potential anti-ulcer activity.

In rats, both Cu(I) and Cu(II) show an irritancy profile not shared with Cu degrees or Zn(II) or Ni(II). The gastric response to Cu(II), i.e. copius fluid and mucus secretion, can protect the stomach from the acute ulcerative effects of aspirin or physical stress administered subsequently.     

Colchicine inhibits stimulated release of gastric histamine but not activation of histidine decarboxylase.

In the rat, gastric mucosal histamine is mobilized and histidine decarboxylase activated by treatment with insulin or pentagastrin. Colchicine pretreatment prevented the histamine release without preventing the enzyme activation. The results suggest a) that histamine release and histidine decarboxylase activation are independent events, and b) that microtubules are involved in the release of histamine.     

Colchicine inhibits stimulated release of gastric histamine but not activation of histidine decarboxylase

Summary In the rat, gastric mucosal histamine is mobilized and histidine decarboxylase activated by treatment with insulin or pentagastrin. Colchicine pretreatment prevented the histamine release without preventing the enzyme activation. The results suggest a) that histamine release and histidine decarboxylase activation are independent events, and b) that microtubules are involved in the release of histamine.