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1. A camptothecin derivative, irinotecan (Cpt-11), is a topoisomerase I inhibitor and has a strong activity against a broad range of human cancer. One of the side-effects of this drug is diarrhoea. Here, we tried to determine the mediator of the irinotecan-induced Cl- secretion which may underlie this diarrhoea, using isolated mucosae of rat distal colon.(More)
We have used Heidenhain-pouch dogs to investigate the effects of (+/-)-5-methoxy-2-{[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulph inyl}-1H-imidazo[4,5-b]pyridine (TU-199), an imidazopyridine derivative, on gastric acid secretion stimulated by histamine, carbachol and tetragastrin. We have also investigated the duration of the antisecretory effect of(More)
Properties of hypotonically-activated Cl- channels in isolated rat hepatocytes were studied by the patch-clamp whole-cell technique. Hypotonic stress (140-150 mosmol kg 1 H2O) induced a hyperpolarization of the membrane of hepatocytes in the presence of an inwardly oriented Cl gradient, but had no effect on the membrane potential in the absence of Cl. An(More)
Gastric enterochromaffin-like (ECL) cells were isolated from rat gastric fundic mucosa by Percoll density-gradient centrifugation and counter-flow elutriation. About 67% of cells in the purified cell suspension were ECL cells, which were reacted with anti-histidine decarboxylase antibody. A23187, a calcium ionophore, at 0.1-10 microM induced histamine(More)
A housekeeping basolateral Cl- channel in rabbit gastric parietal cells (0.3-0.4 pS) is closed by an intracellular application of GTP gamma S. Here, we found a novel GTP gamma S-dependent regulatory mechanism, in which GTP gamma S stimulates intracellular superoxide (O2-) production and the O2- acts as a messenger in the closure of the Cl- channel. Other(More)
The general pharmacological profiles of a novel proton pump inhibitor, (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulfi nyl]- 1H-imidazo[4,5-b]pyridine, TU-199) on the central nervous system, cardiorespiratory system, autonomic nervous system, gastrointestinal system and renal functions were investigated. TU-199 had no effects on general(More)
We studied the effects of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion and gastroduodenal lesions in rats in comparison with those of omeprazole. TU-199 inhibited hog gastric H+, K(+)-ATPase activity and its potency was almost equal to that of omeprazole (IC50 = 6.2 and 4.2 microM, respectively). In vivo, TU-199 inhibited basal(More)
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