Mitigation of stress-induced gastric mucosal lesions by a specific type IV phosphodiesterase inhibitor.
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.
Kato
Sayuri
S
Department of Internal Medicine-1, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Otaka
Michiro
M
Odashima
Masaru
M
Sato
Toshihiro
T
Jin
Mario
M
Matsuhashi
Tamotsu
T
Konishi
Noriaki
N
Watanabe
Sumio
S
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
D010726:Phosphodiesterase Inhibitors; D002927:Cimetidine; D000242:Cyclic AMP; D009195:Peroxidase; D020889:Rolipram