Effects of L-Glutamine on Acetylsalicylic Acid-Induced Gastric Lesions in Normal and Cirrhotic Rats

et al. 1977

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Abstract-The effects of metiamide, a histamine H2-receptor antagonist, and pro pranolol, a beta-adrenergic blocking agent, on gastric secretion were studied in anes thetized dogs. Metiamide, 1.45 mg/kg i.v., markedly inhibited the gastric secretion induced by a continuous i.v. infusion of tetragastrin (8 pg/kg-hr), histamine dihydro chloride (160 pg/kg-hr), or methacholine bromide (100 fig/kg-hr). Propranolol 0.5 or 1.0 mg/kg i.v. produced a significant potentiation of tetragastrin-induced gastric se cretion but no influence on the secretion induced by methacholine. Propranolol at 5 or 10 mg/kg i.v. produced a slight reduction of the tetragastrin-induced secretion and a significant reduction of methacholine-induced secretion. Histamine-induced gastric secretion was not affected by propranolol at either 1 and 10 mg/kg i.v. These findings lend support to the hypothesis that interactions among histamine, gastrin and acetyl choline receptors do occur though the degree would not be the same in all direc tions.Grossman and Konturek (1) have reported a new hypothesis from the effect of meti amide, a histamine H2-receptor antagonist (2), and atropine on gastric secretion in Heidenhain pouch dogs. According to this hypothesis, the parietal cell has separate re ceptors for histamine, gastrin and acetylcholine and these receptors interact. Blockade of the histamine receptors by metiamide changes the properties of the gastrin or acetylcholine receptors to the extent that there is a reduction in the stimulation by gastrin or acetylcholine.However, blockade of the acetylcholine and gastrin receptors by atropine only weakly sup presses histamine receptors, indicating that the degree of interaction would be directionally unequal. Since the beta-adrenergic blocking agent, propranolol, is known to exert various effects on basal or stimulated gastric secretion in rats (3-6), dogs (7,8) and man (9, 10), it was used herein as a pharmacological tool together with metiamide. MATERIALS AND METHODSThirty-eight male mongrel dogs, weighing 8-15 kg, were deprived of food for 24 hr and then anesthetized with pentobarbital Na (30 mg/kg, i.v.). The abdomen was incised and the stomach exposed. The pylorus was ligated and a stainless steel cannula was in troduced into the stomach through the anterior wall and secured tightly around the inserted part with two purse-string sutures. The cannula was brought out through a stab wound in the abdominal wall and the incision was closed. The esophagus was also tied off at the neck region. In order to continuously infuse gastric stimulants and physiological saline

Section: Discussionsupporting

confidence: 88%

Effects of Metiamide and Propranolol on Gastric Secretion in Anesthetized Dogs

et al. 1977

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“…It should be noted that L-glutamine, given together with ASA or TCA, significantly prevented the potentiated development of ASA or TCA lesions in stressed rats, just as was found in pregnant and cirrhotic rats (9,10). Thus, it would appear that ASA may be safely recommended even to persons who are in stress conditions inasmuch as it is given together with L-glutamine.…”

Section: Discussionmentioning

confidence: 86%

“…It was found that stress itself (shock by bleeding) did not cause acute ulcers but resulted in a high occurrence rate of ulcers when coupled with intragastric bile salts (6). We have found that L-glutamine prevented both normal and enhanced development of ASA-induced gastric lesions in normal, pregnant or cirrhotic rats and prevented the reduction of acid and increment of Na+ ions in response to ASA (7)(8)(9)(10). Thus, it was of interest to determine whether or not, 1) ASA or TCA can induce serious damage to the gastric mucosa of stressed rats, 2) L-glutamine inhibits the enhanced development of ASA or TCA lesions under stress, 3) L-glutamine has an effect on the ionic changes in gastric juice as the result of ASA or TCA dosing in either non-stressed or stressed rats.…”

mentioning

confidence: 99%

Effects of L-Glutamine on Acetylsalicylic Acid or Taurocholic Acid-Induced Gastric Lesions and Secretory Changes in Pylorus-Ligated Rats Under Normal or Stress Conditions

et al. 1976

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Abstract-An oral dosing of either acetylsalicylic acid (ASA) or taurocholic acid (TCA) to pylorus-ligated rats subjected to water-immersion stress produced severe damage to the gastric mucosa in contrast to the irritation observed in non-stressed ones. The irritative activity of ASA or TCA on gastric mucosa under stress was dose dependent. Stress itself (23 °C, 7 hr) did not induce any appreciable changes in gastric mucosa of rats. L-glutamine, given together with ASA or TCA, significantly prevented the potentiated development of ASA or TCA-induced gastric lesions in stressed rats. L-glutamine also prevented in varying degrees the reduction of acid and increment of Na+ ion in gastric juice accumulated in stressed rats in response to ASA or TCA.Both acetylsalicylic acid (ASA) and taurocholic acid (TCA) are known to irritate gastric mucosa and to evoke back diffusion of acid through the broken barrier both in man and experimental animals (1-4). In addition, ASA is reported to induce much more severe damage to the gastric mucosa of experimental animals when they are exposed to stress conditions as compared to damage under normal conditions (5). It was found that stress itself (shock by bleeding) did not cause acute ulcers but resulted in a high occurrence rate of ulcers when coupled with intragastric bile salts (6). We have found that L-glutamine prevented both normal and enhanced development of ASA-induced gastric lesions in normal, pregnant or cirrhotic rats and prevented the reduction of acid and increment of Na+ ions in response to ASA (7-10). Thus, it was of interest to determine whether or not, 1) ASA or TCA can induce serious damage to the gastric mucosa of stressed rats, 2) L-glutamine inhibits the enhanced development of ASA or TCA lesions under stress, 3) L-glutamine has an effect on the ionic changes in gastric juice as the result of ASA or TCA dosing in either non-stressed or stressed rats. MATERIALS AND METHODSMale Donryu strain rats, 230-240 g, were deprived of food for 24 hr after which, under ether anesthesia, the pylorus was ligated.Under normal conditions: Either ASA 16. 40 or 100 mg/kg suspended in 1 carhoxy methylcellulose (CM-IC) solution or TCA 30, 100 or 300 mg/kg dissolved in saline solution

“…We have already reported the marked inhibitory effect of L-glutamine on acetylsalicylic acid (ASA)-induced gastric irritation in normal, cirrhotic or pregnant rats, or in rats with a chronic gastric ulcer (1)(2)(3)(4). It was experimentally determined that L-glutamine produces a dose-dependent inhibition of acid back diffusion in response to ASA in the rat stomach (2)(3)(4)(5).…”

mentioning

confidence: 99%

“…It was experimentally determined that L-glutamine produces a dose-dependent inhibition of acid back diffusion in response to ASA in the rat stomach (2)(3)(4)(5). As dogs are frequently used in the study of gastric problems related to ASA (6-9), our present work was an attempt to determine the effects of L-glutamine in this species.…”

mentioning

confidence: 99%

Effects of L-Glutamine on Acetylsalycylic Acid Induced Gastric Lesions and Acid Back Diffusion in Dogs

et al. 1976

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Abstract-Effects of L-glutamine on acetylsalicylic acid (ASA)-induced gastric mucosal lesions were studied in mongrel dogs. It was confirmed that when oral ASA at 1.0 or 2.0 g per dog is given in two divided doses, there is severe and consistent dose-dependent mucosal damage in the glandular portion of the stomach in fasted dogs. However, when L-glutamine 2.0 or 4.0 g per dog in two divided doses is given concomitantly with ASA 2.0 g per dog orally, the gastric irritation is significantly inhibited. Instillation of 20 mM of ASA in 100 mM HCl solution into the Heidenhain pouch of Beagle dogs produced a significant loss of H+ from the pouch and a gain of Na+ in the lumen com pared with ASA-free controls.When L-glutamine (100 mM) was given concomitantly with ASA (20mM) into the pouch, changes of electrolyte fluxes in response to ASA alone were significantly suppressed. However, 50 mM of L-glutamine had no appreciable effect on acid back diffusion caused by ASA 20 mM. The amino acid itself had little effect on the ionic movement in the pouch. Gross bleeding from the pouch treated with ASA was never observed with the concomitant dosing of ASA and L-glutamine 50 or 100 mM.We have already reported the marked inhibitory effect of L-glutamine on acetylsalicylic acid (ASA)-induced gastric irritation in normal, cirrhotic or pregnant rats, or in rats with a chronic gastric ulcer (1-4). It was experimentally determined that L-glutamine produces a dose-dependent inhibition of acid back diffusion in response to ASA in the rat stomach (2-5). As dogs are frequently used in the study of gastric problems related to ASA (6-9), our present work was an attempt to determine the effects of L-glutamine in this species. This report contains data on the potent effect of this amino acid in preventing the noxious effect of ASA on the gastric mucosa in normal dogs and on the acid back diffusion in response to ASA in the stomach of Heidenhain pouch Beagle dogs. MATERIALS AND METHODSASA -lesion formation: Thirty-six male mongrel dogs, weighing 8-10 kg, were deprived of food but allowed free access to water from 10:00 a.m. until the end of the experiments.