Enhanced prostaglandin synthesis in the parturient rat uterus and its effects on myometrial oxytocin receptor concentrations.
We measure oxytocin (OT) responsiveness and prostaglandins (PGs) synthesis in uteri of 19, 20, 21 and 22-day pregnant and 2-day postpartum rats to determine whether the enhanced OT sensitivity and PG synthesis in the parturient uterus is the result of a higher cyclooxygenase activity. We also investigated the effects of suppression of PG synthesis on OT responsiveness and OT receptor in 22-day and 23-day pregnant rats. PG productions (PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 in microsomal fractions were quantitated by radio- immunoassays (RIAs). OT receptor concentrations were measured in plasma membrane fractions by radioligand-receptor binding assays. Naproxen sodium was used to inhibit endogenous PG synthesis. We found a close temporal relationship between enhanced OT responsiveness and increased uterine PGE2 alpha synthesis, but no significant difference in cyclooxygenase activities among the microsomes prepared from uteri of different gestational ages. Suppression of PG synthesis attenuated OT responsiveness and markedly reduced OT binding sites, from 242 to 78 fmol/mg protein. There was no change in the binding affinity. These findings suggest that PG stimulates OT receptor formation which leads to enhanced OT responsiveness. The increase in PG production is not mediated by a higher cyclooxygenase activity.
Chan
W Y
WY
Department of Pharmacology, Cornell University Medical College, New York, New York 10021.
D015121:6-Ketoprostaglandin F1 alpha; D000818:Animals; D015237:Dinoprost; D015232:Dinoprostone; D005260:Female; D007743:Labor, Obstetric; D008861:Microsomes / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D009288:Naproxen / Q000494:pharmacology; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D018045:Receptors, Oxytocin; D013929:Thromboxane B2 / Q000096:biosynthesis; D014590:Uterine Contraction; D014599:Uterus / Q000378:metabolism*
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; D013929:Thromboxane B2; D009288:Naproxen; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone