title: Mitigation of stress-induced gastric mucosal lesions by a specific type IV phosphodiesterase inhibitor.
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.
authors.affiliation: Department of Internal Medicine-1, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Kato
authors.forename: Michiro
authors.initials: M
authors.lastname: Otaka
authors.forename: Masaru
authors.initials: M
authors.lastname: Odashima
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sato
authors.forename: Mario
authors.initials: M
authors.lastname: Jin
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Matsuhashi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Konishi
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology; D007101:Immersion / Q000009:adverse effects; D007263:Infusions, Parenteral; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013276:Stomach Ulcer / Q000188:drug therapy*; D013315:Stress, Psychological
chemical_list: D010726:Phosphodiesterase Inhibitors; D002927:Cimetidine; D000242:Cyclic AMP; D009195:Peroxidase; D020889:Rolipram