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- W2026903810 abstract "Misoprostol (Miso) produces a mild, transient diarrhea in some patients, which is believed to be partly due to intraluminal fluid accumulation. To better understand this diarrheagenic action, we compared the effects of Miso, its 4 stereoisomers (11R16R, 11R16S, 11S16S, 11S16R), misoprostol free acid (Miso-FA), and 16,16-dimethyl PGE2 (dmPGE2) on rat colonic electrolyte transport in vitro. Increases in short-circuit current (lsc) were measured (after serosal addition) in segments of mucosa stripped of muscularis and mounted in Ussing chambers. The rank order of apparent potencies, in terms of threshold, were (μM): 11R, 16S (1.2) ≈ dmPGE2 (1.0)> Miso-FA (10.0) ∼ Miso ⪢ 11R, 16R; 11S, 16R; 11S, 16S (all inactive at 100 μM). The response to dmPGE2 and Miso was attenuated in the presence of the Na+/K+/Cl− co-transport inhibitor bumetanide (100 μM). Pretreatment with atropine (0.1 μM) did not affect the lsc response to Miso, Miso-FA, or dmPGE2. Tetrodotoxin partially attenuated (39±9% inhibition) the response to Miso-FA, but did not affect Miso or dmPGE2. In conclusion, Miso increases Cl− secretion across rat colonic mucosa through a direct action on epithelial cells. The activity resides in the 11R, 16S isomer, thus implying a stereospecific interaction at PGE receptors. The effect of Miso to stimulate epithelial Cl− secretion might contribute to its diarrheagenic action in vivo." @default.
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- W2026903810 date "1993-09-01" @default.
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- W2026903810 title "Stereospecific actions of misoprostol on rat colonic electrolyte transport" @default.
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- W2026903810 doi "https://doi.org/10.1016/0090-6980(93)90005-r" @default.
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