Prostaglandin F2 alpha stimulates inositol phosphate production in human pregnant myometrium.
We examined the effect of prostaglandin F2 alpha (PGF2 alpha) on phosphoinositide (PI)-hydrolysis in the outer layer of the human myometrium at the end of pregnancy. After pretreatment of myometrial explants with a cyclo-oxygenase inhibitor (indomethacin), the PGF2 alpha dose-response curve was shifted to the left and a maximal level of PGF2 alpha-induced IP accumulation was reached. In contrast, the well-known OT-induced IP accumulation was decreased in the presence of indomethacin, whereas potency was unchanged. Incubation of the myometrial explants with calcium-depleted medium, not only decreased the basal IP production but completely abolished the OT- and PGF2 alpha-induced IP accumulation. A L-type calcium channel inhibitor, verapamil 100 microM, significantly decreased PGF2 alpha-induced total inositol production whereas it had no effect on OT-response, suggesting that the first event of PGF2 alpha action is the activation of a calcium channel. These results point to marked differences in the mechanisms by which OT and PGF2 alpha exert their contractile effects in human myometrium at the end of pregnancy.
Maka
F D
FD
INSERM. U. 361, Reproduction et Physiopathologie Obstetricale, Maternite Baudelocque, Paris, France.
Breuiller-Fouche
M
M
Geny
B
B
Ferre
F
F
D002118:Calcium / Q000502:physiology; D046508:Culture Techniques; D015237:Dinoprost / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis*; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy / Q000378:metabolism*
D007295:Inositol Phosphates; D010121:Oxytocin; D015237:Dinoprost; D002118:Calcium; D007213:Indomethacin