Increased microvascular permeability in early stage of dextran sulfate sodium-induced colitis: its interaction with lansoprazole binding sites.
To clarify the microvascular changes and the effector sites of lansoprazole during the formation of colitis, the dextran sulfate sodium (DSS)-induced colitis was induced by the oral administration for 3 and 7 days. The alteration of the microvascular permeability was estimated by the intraaortic infusion of FITC-dextran. The effector sites of 3H-lansoprazole were examined by the intraaortic infusion of the radiolabelled compound and the autoradiographic procedure of water-soluble compounds. As a result, marked increase of the microvascular permeability was detected three days after DSS treatment near the inflammatory cells in the tip portion of the colonic mucosa. 3H-lansoprazole in the control rat colon was localized in the goblet cells, while in DSS-treated rats, 3H-lansoprazole was accumulated in the cytoplasm of the mesenchymal cells, and most of them coincided with polymorphonuclear leucocytes and macrophages.
Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University, Sanno Hospital, Tokyo, Japan. nakamuram@pharm.kitasato-u.ac.jp
Masahiko
M
Nakamura
Maki
M
Asada
Hidenori
H
Matsui
Norifumi
N
Hibi
Kanji
K
Tsuchimoto
Jun
J
Inoue
Masaya
M
Oda
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D001665:Binding Sites; D002199:Capillary Permeability / Q000187:drug effects*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism; D016264:Dextran Sulfate; D020397:Goblet Cells / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D064747:Lansoprazole; D008264:Macrophages; D009504:Neutrophils; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors; D051381:Rats; D017208:Rats, Wistar
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D016264:Dextran Sulfate; D009853:Omeprazole