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- W2002472904 abstract "Naturally occurring and synthetic prostaglandins acting at EP type receptors have a number of physiological actions, including cytoprotective and antisecretory effects, that are therapeutically useful. In addition they can produce other effects, such as diarrhea. It is possible that these actions are mediated by different EP receptor subtypes. The actions of a subtype-selective prostaglandin agonist has suggested that diarrhea is not due to activity at the EP3 receptor, while cytoprotection and antisecretory actions may be. The recent development of a bioavailable EP1 antagonist, SC-51089, has made it possible to examine this more directly. SC-30249, the active isomer of misoprostol, protects against indomethacin-induced gastric lesions and produces diarrhea in rats. SC-51089, ig, shifted the dose-response curve for SC-30249-induced diarrhea significantly to the right. ED50 values (assessed at 5 hr following administration of SC-30249) were 13.8 μ/kg (0.036 μmol/kg) for SC-30249 alone and 110.8 μg/kg (0.290 μmol/kg) for SC-30249 plus SC-51089. This antagonism of diarrhea was overcome by higher doses of SC-30249. SC-30249 dosedependently inhibited gastric lesions induced by indomethacin (ED50 = 3.4 μg/kg, 0.009 μmol/kg, ig). SC-51089 did not reduce the cytoprotective effects of SC-30249 (ED50 = 1.1 μg/kg, 0.003 μmol/kg, ig, SC-30249 in combination with SC-51089). These results are consistent with the hypothesis that the EP1 receptor subtype mediates the diarrheagenic effect of EP receptor agonists, but not their cytoprotective actions. These results provide a mechanistic basis for cytoprotective prostaglandins with greatly reduced side effects. © Wiley-Liss, Inc." @default.
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- W2002472904 title "EP1 receptor antagonist blocks the diarrheagenic, but not cytoprotective, actions of a synthetic prostaglandin" @default.
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- W2002472904 doi "https://doi.org/10.1002/ddr.430340106" @default.
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