Anti-Ulcer effect of FK 506, immunosuppressive agent, in rats

Zeniya, Akira; Otaka, Michiro; Kuwabara, Toshiyuki; Fujimori, Shusel; Otani, Setsuya; Masamune, Osamu

doi:10.1007/bf02358382

Cited by 3 publications

(7 citation statements)

References 3 publications

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“…4,5) It was also reported earlier that the immunosuppressive agent tacrolimus prevented gastric mucosal lesions. 6,7) In the peptic ulcer condition mast cells play an important key role. Activated mast cells release various biochemical mediaters like cytokines (TNF, interleukin, interferon, leukotriene etc.…”

Section: Introductionmentioning

confidence: 99%

Activity of Tacrolimus: An Immunosuppressant, in Pyloric Ligation Induced Peptic Ulcer in Rat

Sood

Muthuraman

2009

YAKUGAKU ZASSHI

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The eŠect of tacrolimus (FK506) on peptic ulcer was evaluated using pyloric ligation (PL) model in rats. Tacrolimus was administered orally at diŠerent doses (1, 2 and 3 mg/kg) and it showed a gastric ulcer healing eŠect in a dose dependent manner. Gastric volume, total and free acidity and ulcerative index parameters were reduced in the tacrolimus treated rats as compared to pyloric ligated rats. The higher dose (3 mg/kg) treated group produced signiˆcant results similar to that of the ranitidine (50 mg/kg) treated group. Pretreatment with tacrolimus also produced signiˆcant (p＜ 0.05) reduction in TBARS, total calcium, TNF-a, IL-8 and MPO whereas it showed an increase in GSH level at higher dose. The anti-secretory and anti-ulcerative eŠect of tacrolimus may be due to immunosuppressive actions by inhibition of calcineurin and the oxidative pathway. It can be concluded that tacrolimus can play an important role in the treatment of peptic ulcer disorder to improve the quality of life.

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Section: Introductionmentioning

confidence: 99%

Activity of Tacrolimus: An Immunosuppressant, in Pyloric Ligation Induced Peptic Ulcer in Rat

Sood

Muthuraman

2009

YAKUGAKU ZASSHI

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“…Although it has been reported that FK506 prevents gastric ulcer formation induced by water‐immersion stress, hydrochloride or indomethacin, 1–3 through attenuation of leucocyte–endothelium adherence and inhibition of MPO activities, 1 , 2 the mechanisms of the anti‐ulcer action of FK506 have not been confirmed. In this study, we demonstrated that FK506 effectively reduced acid secretion at the minimal dose of 0.5 mg/kg, although this dose of FK506 is much higher than that in clinical usage as an immunosuppressant.…”

Section: Discussionmentioning

confidence: 97%

“…It has been reported that tacrolimus hydrate (FK506), an immunosuppressive agent, prevents gastric ulcer formation induced by water‐immersion stress, hydrochloride or indomethacin 1–3 . Although the preventive effect of FK506 may derive from the suppression of cytokines, 1 , 2 myeloperoxidase (MPO) activities 1 and neutrophils, 1 , 2 the mechanism of protective effect of FK506 on gastric ulcer formation has not been ascertained.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of CN (protein phosphatase‐2B) suppresses Ca²⁺‐mediated acid secretion in rats

Itoh

Otaka

Odashima

et al. 2002

Aliment Pharmacol Ther

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Background and aim: It has been suggested that CN (calcineurin, protein phosphatase‐2B) regulates signal transduction, particularly in various secretory cells. In this study, we examined whether CN plays a role in stimulus‐secretion coupling of gastric parietal cells. Materials and methods: Localization of CN in gastric epithelial cells was examined immunohistochemically. The role of CN in the acid secretion pathway of gastric parietal cells was assessed by evaluating the effect of FK506, a specific inhibitor of CN, on gastric acid secretion in pylorus‐ligated rats. In addition, the effect of FK506 on secretagogue (carbachol, tetragastrin and histamine)‐stimulated acid secretion was investigated in lumen‐perfused rats. Results: CN was specifically expressed in gastric parietal cells and chief cells of the gastric mucosal epithelium immunohistochemically. FK506 dose‐dependently inhibited gastric acid secretion in pylorus‐ligated rats. In lumen‐perfused rats, FK506 completely inhibited acid secretion prestimulated by carbachol and tetragastrin, agonists known to increase cytosolic Ca2+, but did not affect acid secretion prestimulated by histamine. Conclusions: Our findings demonstrate that FK506 has a potent antisecretory effect in parietal cells through inhibition of only Ca2+‐mediated acid secretion pathways. As FK506 is known to specifically inhibit CN, which plays an important role in signal transduction in various secretory cells, protein dephosphorylation signalling might also be crucial for gastrin and M3 muscarine receptor‐mediated stimulation of proton pump.

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“…*P Ͻ 0.01, **P ϭ 0.001; ***P Ͻ 0.001 compared with control group and myeloperoxidase content. [2][3][4][5] Although various mechanisms are involved in the pathogenesis of water immersion stress-induced gastric lesion, gastric acid secretion is thought to be one of the most important factors. 8,9 In addition, it is well established that various antisecretory agents, such as H 2 -receptor antagonists and proton pump inhibitors, prevent gastric lesions induced by water-immersion stress.…”

Section: Fig 2 Effects Of Cyclosporin a On Ulcer Formation Induced Bymentioning

confidence: 99%

“…1 Recently it has been reported that the immunosuppressive agents cyclosporin A and FK-506 prevented experimental gastric mucosal lesions. [2][3][4][5] Although it has been speculated that the preventive effects were derived from the suppression of cytokine synthesis and neutrophil infiltration, the mechanisms have not been well understood. 2,3 In this study, we investigated the effects of cyclosporin A on gastric ulcer formation induced by Gastric juices were collected by the pylorus ligation method.…”

mentioning

confidence: 98%

Effects of cyclosporin A on water-immersion stress-induced gastric lesion and gastric secretion in rats

Odashima

Otaka

Ito

et al. 2000

Journal of Gastroenterology

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Cyclosporin A is an immunosuppressive agent which is well known as a specific inhibitor of calcineurin (protein phosphatase 2B). In this study, we investigated the effects of cyclosporin A on water-immersion stress-induced gastric ulcer formation and gastric acid secretion in rats. We also examined the localization of calcineurin immunohistochemically. Calcineurin was specifically expressed in gastric parietal cells and chief cells of the gastric mucosa. The intraperitoneal administration of cyclosporin A dose-dependently suppressed the development of gastric mucosal lesions induced by water-immersion stress and inhibited gastric acid secretion, as assessed by pylorus ligation. These results indicated that calcineurin may play an important role in gastric acid secretion.

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Anti-Ulcer effect of FK 506, immunosuppressive agent, in rats

Cited by 3 publications

References 3 publications

Activity of Tacrolimus: An Immunosuppressant, in Pyloric Ligation Induced Peptic Ulcer in Rat

Activity of Tacrolimus: An Immunosuppressant, in Pyloric Ligation Induced Peptic Ulcer in Rat

Inhibition of CN (protein phosphatase‐2B) suppresses Ca²⁺‐mediated acid secretion in rats

Effects of cyclosporin A on water-immersion stress-induced gastric lesion and gastric secretion in rats

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Anti-Ulcer effect of FK 506, immunosuppressive agent, in rats

Cited by 3 publications

References 3 publications

Activity of Tacrolimus: An Immunosuppressant, in Pyloric Ligation Induced Peptic Ulcer in Rat

Activity of Tacrolimus: An Immunosuppressant, in Pyloric Ligation Induced Peptic Ulcer in Rat

Inhibition of CN (protein phosphatase‐2B) suppresses Ca2+‐mediated acid secretion in rats

Effects of cyclosporin A on water-immersion stress-induced gastric lesion and gastric secretion in rats

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Inhibition of CN (protein phosphatase‐2B) suppresses Ca²⁺‐mediated acid secretion in rats