Examination of the effects of piriprost (U-60,257B) on alkaline phosphatase activity of rat endometrial stromal cells in vitro.
Previously, piriprost (U-60,257B; an inhibitor of leukotriene (LT) synthesis) was shown to increase alkaline phosphatase (ALP) activity in cultured endometrial stromal cells (1). The present study investigated the mechanism of action of piriprost in this system. Sensitized rat endometrial stromal cells were isolated and cultured for up to 72 hr with various treatments. Piriprost (100 microM) was found to decrease 5-hydroxyeicosatetraenoic acid (a 5-lipoxygenase product) by 53% after 72 hr which provided evidence that 5-lipoxygenase was being inhibited by piriprost. Lactate dehydrogenase (LDH) activity confirmed that piriprost was not toxic to the cells. The possibility of piriprost acting in an analogous manner with that of PGs was examined. Three microM PGE2 or 20 microM carba-prostacyclin (CP), an analogue of PGI2, maximally increased (p less than 0.01) ALP activity at 72 hr and the further addition of 100 microM piriprost to PGE2 or CP caused an additional, additive increase in ALP activity. This indicated that the mechanism of action of piriprost was probably different from that of PGE2 or PGI2. The possibility that piriprost was shunting arachidonic acid into PG production was examined. Ten microM indomethacin (an inhibitor of PG synthesis) caused a decrease (p less than 0.01) in ALP activity and a 99% reduction in PGE2 at 72 hr. The effects of the combination of 100 microM piriprost and 10 microM IM were statistically additive, suggesting that the effects of piriprost were not due to an increase in PG production. These studies suggest that the effects piriprost on possible in vitro decidualization may be due to inhibition of 5-lipoxygenase.
Cejic
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Department of Physiology, University of Western Ontario, London, Canada.
Kennedy
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D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D006893:Hydroxyeicosatetraenoic Acids; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; C026678:carboprostacyclin; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D015232:Dinoprostone; C035296:piriprost