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Am J Physiol Gastrointest Liver Physiol 281: G1151-G1157, 2001;
0193-1857/01 $5.00
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Vol. 281, Issue 5, G1151-G1157, November 2001

Nitric oxide donors retard wound healing in cultured rabbit gastric epithelial cell monolayers

Tuula Kiviluoto1,2, Sumio Watanabe2, Miyoko Hirose2, Nobuhiro Sato2, Harri Mustonen1, Pauli Puolakkainen1, Mikko Rönty1, Tuula Ranta-Knuuttila1, and Eero Kivilaakso1

1 Department of Surgery, Helsinki University Central Hospital, 00029 Helsinki, Finland; and 2 Department of Gastroenterology, Juntendo University Central Hospital, School of Medicine, Tokyo 113, Japan

Effects of nitric oxide (NO) on gastric wound healing were investigated in primary rabbit gastric epithelial cell cultures. We analyzed the speed of cell migration, proliferation, and apoptosis after creating a round wound on the cell cultures. The monolayers were incubated with or without the NO donor sodium nitroprusside, oxatriazolimine 1,2,3,4-oxatriazolium, 5amino-3-(3,4-dichlorophenylchloride), or the peroxynitrite generator 3-morpholinosydnomine-N-ethylcarbamide. The possible role of cGMP as a second messenger of NO was investigated with 8-bromo-cGMP. The role of O<UP><SUB>2</SUB><SUP>−</SUP></UP>· was evaluated using diethyldithiocarbamate and pyrogallol. The effects of superoxide dismutase and allopurinol were also investigated. NO inhibited the speed of cell migration and proliferation and induced cell apoptosis in a dose- and time-dependent manner. The effects were augmented with O<UP><SUB>2</SUB><SUP>−</SUP></UP>· generators and ameliorated by O<UP><SUB>2</SUB><SUP>−</SUP></UP>· scavengers, whereas cGMP had no significant effect on wound healing. NO donors retard gastric wound healing by inhibiting migration and proliferation and inducing cell apoptosis. These effects do not seem to be mediated via cGMP, but O<UP><SUB>2</SUB><SUP>−</SUP></UP>· or peroxynitrites may be involved.

gastric epithelium; cell migration; cell proliferation; apoptosis; peroxynitrite; hydroxyl radicals; superoxide; guanosine 3',5'-cyclic monosphosphate


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