RU486 and calcium fluxes in human spermatozoa.
RU486 decreases the intracellular free calcium concentration in human spermatozoa incubated in capacitation medium. We investigated the calcium fluxes that this progesterone antagonist acts on. We found that 10(-5) M RU486 slowed down the basal calcium influx while progesterone accelerated it. Moreover, in the same way as RU486 inhibits the calcium increase promoted by progesterone, it inhibited the calcium influx stimulated by 10(-6) M thapsigargin, an endoplasmic reticulum Ca(2+)-ATPase inhibitor. So we speculated that RU486 does not necessarily compete for the same binding sites as progesterone to exert its inhibitory action. In the absence of extracellular calcium, pretreatment by 10(-5) M RU486 decreased the peak of [Ca2+]i released by 5 microM ionomycin. This indicates that RU486 could also act at the membrane level of some intracellular organelles of calcium storage.
Laboratoire d'Histologie-Embryologie, Université Paris XI, Centre Hospitalier, Le Kremlin-Bicetre, France.
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Serres
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Yang
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Jouannet
D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008345:Manganese / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology*; D015388:Organelles / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D013997:Time Factors
D013729:Terpenes; D015735:Mifepristone; D008345:Manganese; D011374:Progesterone; D015759:Ionomycin; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium