Susumu Okabe

Effects of cimetidine, a histamine H2-receptor antagonist, on various experimental gastric and duodenal ulcers.

The effects of cimetidine, a new histamine H2-receptor antagonist, on the development of experimental gastric and duodenal ulcers were studied. It was found that either by the oral, intraduodenal, or intraperitoneal route this agent had a marked inhibitory activity on stress-, aspirin-, indomethacin-, or histamine-induced gastric ulcers in rats and guinea pigs. The effects of cimetidine on stress-, aspirin-, and indomethacin-induced gastric ulcers were dose-dependent in many cases. Pylorus-ligation ulcers, reserpine-or serotonin-induced gastric ulcers were little influenced by cimetidine. Duodenal ulcers induced by continuous infusion of carbachol-histamine were significantly inhibited by a simultaneous infusion of cimetidine. An analysis of gastric contents in pylorus-ligated rats after stressing indicated a decreased volume and acid output as the result of intraduodenal cimetidine treatment. In contrast, cimetidine exerted little influence on gastric secretion in rats treated with aspirin or in guinea pigs treated with histamine. Thus, the mechanism of action of cimetidine in preventing gastric or duodenal ulcers is likely to occur by suppression of gastric secretory function in a duodenal ulcer model but by suppression of other unknown ulcerogenic factors in gastric ulcer models.

Effects of cimetidine and atropine sulfate in gastric secretion and healing of gastric and duodenal ulcers in rats

Cimetidine, a new histamine H2-receptor antagonist (50 or 100 mg/kg) and atropine sulfate (15 mg/kg) given intraduodenally, markedly inhibited gastric secretion in pylorus-ligated rats. Cimetidine (100 or 200 mg/kg/day) given for 10 or 12 consecutive days orally in two divided doses, significantly promoted the healing rate of both gastric and duodenal ulcers induced in rats. Atropine (30 mg/kg/day) also significantly accelerated the healing of duodenal ulcers but failed to affect gastric ulcers.

A new model of stress ulcer in the rat with pylorus ligation and its pathogenesis.

Water-immersion stress for 7, 14, or 20 hr consistently induced linear or punctate stress ulcers (mucosal erosions) in the corpus of the stomach in intact rats. When the pylorus of the stomach had been ligated prior to stressing, the stress ulcers changed their morphological feature (mainly punctate and in one place elongated) and location (both in corpus and antrum). Histologically, the stress ulcer developed in the proximal antrum of pylorusligated rats and penetrated into the muscularis mucosa. Sodium bicarbonate, chlorpromazine, hexamethonium, atropine, metiamide, and bilateral vagotomy markedly inhibited the stress ulcers which developed in the pylorus-ligated rats. Phentolamine and propranolol hardly affected the development of stress ulcers. Amylopectine evoked a new type of stress ulcer in the corpus when it was given to the pylorus-ligated rats.

Inhibitory effect ofl-glutamine on gastric irritation and back diffusion of gastric acid in response to aspirin in the rat

Abstractl-Glutamine given orally at 750 mg/kg significantly reduced the formation of gastric mucosal lesions induced by aspirin at 100 mg/kg at 1, 3, and 7 hours in pylorus-ligated rats.l-Glutamine markedly inhibited the loss of H+ and a corresponding increment of Na+ through the aspirin-damaged mucosal barrier, which suggests inhibition of acid back diffusion as the mechanism of action. In vagotomized rats, the diffusion of H+ from the instilled acid solution into the gastric mucosa and outflux of Na+ from the mucosa into the lumen was so strong that aspirin could not show any acceleration of a back diffusion of H+ in contrast to the aspirin-free group. However,l-Glutamine given with or without aspirin inhibited the back diffusion of H+ instilled into the vagotomized rat stomach.

Studies of the mechanisms involved in the production of stress and stress-atropine ulcers in rats

Abstract The mechanism of the production of gastric ulcers induced in atropinized rats under stress was investigated and compared with that of stress-induced ulcers (S-ulcer). The etiology of the stress-atropine ulcer (A-ulcer) was found to be mainly due to the participation of adrenergic nerves since the ulceration was inhibited by ganglion blockers, adrenergic blockers, and reserpine, though vagotomy also inhibited the formation of A-ulcer. On the other hand, S-ulcer was inhibited by certain nervous system depressants, ganglion blockres, vagotomy and atropine; therefore, a certrally mediated cholinergic factor was suggested to be the main factor in the ulceration.

Effects of Acetylsalicylic Acid (ASA), ASA plus L-Glutamine and L-Glutamine on Healing of Chronic Gastric Ulcer in the Rat

A chronic gastric ulcer model was produced in rats by the subserosal injection of 20% acetic acid solution (0.015 ml) in order to examine whether (1) acetylsalicylic acid (ASA) irritates the chronic gastric ulcer in active or healed or diminished stage, (2) L-glutamine, given together with ASA, inhibits the adverse effect of ASA. Oral ASA 200 mg/kg/day, given in two divided doses for 10 consecutive days, apparently delayed the healing of the gastric ulcer and irritated the healed ulcer to reulcerate. L-Glutamine, 1,500 mg/kg/day, which was given together with ASA in two divided doses, markedly protected the gastric ulcer both in active and healed stages from the deleterious activity of ASA.

Inhibitory effects of L‐glutamine on the aspirin‐induced gastric lesions in the rat

The effects of an amino acid, L‐glutamine, on aspirin‐induced gastric lesions and gastric secretion were studied in either intact or pylorus‐ligated rats. L‐Glutamine had a pronounced inhibitory effect on gastric lesions induced by aspirin administered by oral, intraperitoneal, or intraduodenal routes to intact or pylorus‐ligated rats. By the oral route the inhibition was dose‐related. However, L‐glutamine given either intraduodenally or intraperitoneally did not show any appreciable effects on gastric lesions induced by orally administered aspirin in pylorus‐ligated rats. One mechanism of L‐glutamine protection was inhibition of a back diffusion of gastric acid caused by aspirin and this was demonstrated in pylorus‐ligated rats. The reduction in H+ and increase in Na+ concentrations in the lumen caused by aspirin was returned to normal by increasing doses of L‐glutamine. In addition, L‐glutamine was considered to inhibit the back diffusion of acid caused by pylorus ligation per se, because the amino‐acid produced an increment of H+ and reduction of Na+ and K+ in comparison with the control group. The role of pepsin on L‐glutamine protection was negligible.

Effects of L-glutamine on various gastric lesions in rats and guinea pigs.

Effects of L-glutamine on gastric lesion models in rats and guinea pigs were studied. Shay ulceration in rats was not inhibited by oral L-glutamine. Although stress-induced gastric lesions in intact rats were not inhibited by L-glutamine, a strong antagonism of gastric lesions was induced in pylorus-ligated rats under the same stress by the amino acid. Histamine-induced gastric lesions in intact rats and guinea pigs were also markedly inhibited by L-glutamine. L-Glutamine inhibited the gastric lesions in rats induced by compound 48/80 but not significantly. Reserpine- or serotonin-induced gastric lesions in rats were not affected by L-glutamine. The mechanism of L-glutamine protection was discussed.

Effects of cimetidine on healing of chronic gastric and duodenal ulcers in dogs

The effects of cimetidine on healing of gastric and duodenal ulcers induced in mongrel dogs were studied. Gastric ulcers were produced by subserosal injection of acetic acid solution and duodenal ulcers by topical application of acetic acid on the serosal surface of the duodenum. Oral treatment with cimetidine, 450 mg/dog/day in three divided doses for 14 days, produced a remarkable acceleration of healing of duodenal ulcers but exerted little influence on gastric ulcers.

Effects of antacid, antipeptic and anticholinergic agents on the development and healing of duodenal ulcers in the rat.

Early stages of the duodenal ulcer induced by acetic acid in rats were studied. The necrotized mucosa in the duodenum gradually progressed to a deep ulcer by the 5 postoperative days, then the ulcer reduced in size and depth considerably by the 10th day. Aluminum hydroxide, amylopectine sulfate and atropine sulfate, given for 5 days beginning immediately after the operation, inhibited the ulceration weakly but lessened the incidence of rats with deep ulcer. Aluminum hydroxide and amylopectine sulfate, given for 8 days beginning 1 day after the operation, significantly accelerated the healing of the duodenal ulcer, i.e., these agents diminished the ulcerated area and its depth. However, atropine sulfate diminished the depth of ulcer crater while the ulcerated area remained unchanged in comparison with that of control group.