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.
Nakamura
Masahiko
M
Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University, Sanno Hospital, Tokyo, Japan. nakamuram@pharm.kitasato-u.ac.jp
Asada
Maki
M
Matsui
Hidenori
H
Hibi
Norifumi
N
Tsuchimoto
Kanji
K
Inoue
Jun
J
Oda
Masaya
M
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