Mitigation of Stress-Induced Gastric Mucosal Lesions by a Specific Type IV Phosphodiesterase Inhibitor

Sayuri Kato; Michiro Otaka; Masaru Odashima; Toshihiro Sato; Mario Jin; Tamotsu Matsuhashi; Noriaki Konishi; Sumio Watanabe
March 2007
Digestive Diseases & Sciences;Mar2007, Vol. 52 Issue 3, p711
Academic Journal
Abstract??Inhibition of type IV phosphodiesterase (PDE4) activity is beneficial in various inflammations. However, the effect of phosphodiesterase inhibitors on the development of stress-induced gastric mucosal lesions has not been reported. In the present study, we examined the effect of a specific PDE4 inhibitor (rolipram) on stress-induced gastric mucosal lesions. Rats were exposed to water-immersion stress with or without pretreatment with rolipram. Ulcer index and myeloperoxidase activity of the gastric mucosa were evaluated. Gastric mucosal lesions and mucosal myeloperoxidase activity were suppressed by treatment with rolipram without acid suppression. The effect of intraperitoneal administration of 2.5?mg/kg rolipram on suppression of mucosal lesions was almost equal to that of treatment with 200?mg/kg cimetidine. We demonstrated that a specific PDE4 inhibitor has a potent anti-ulcer effect presumably mediated by an increment in intracellular cAMP in inflammatory cells, in which this enzyme is abundantly and specifically expressed.


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