Relationship Between the Uterotonic Action of Oxytocin and Prostaglandins: Oxytocin Action and Release of PG-Activity in Isolated Nonpregnant and Pregnant Rat Uteri

Abstract

The relationship between the uterotonic action of oxytocin (OT) and prostaglandins (PC) was studied on isolated rat uteri. We found that specific OT antagonist had no effect on the uterine response to PG under similar condition when the response to an equi-potent dose of OT was completely suppressed. Effective PG synthetase inhibitory doses of indomethacin and diclofenac sodium had no significant effect on the uterine response to OT or PG. These findings indicate that the myometrial receptors for OT and PG are functionally separate and distinct and that the uterotonic action of OT is independent of PG participation. Parturient uterus is extremely sensitive to OT action. One possible mechanism for this sensitization may be associated with an enhanced PG synthesis and release induced by OT. We measured the basal PG content and release in isolated uteri from nonpregnant, nonpregnant and estrogen treated rats, and from rats in the last four days of pregnancy. We found that estrogen increased the PG content and release in nonpregnant rat uteri. The absolute levels, however, remained low, less than 50 ng/uterus and 25 ng/uterus/hr. In late pregnant uteri, PG synthesizing capacity increased progressively reaching an enormous peak, an increase of more than 1000 percent on the expected day of delivery. OT, 1.0 mU/ml, caused contractions in both nonpregnant and pregnant uteri. The PG content and release of the nonpregnant uteri were not significantly affected by OT. This is consistent with our finding that the uterotonic action of OT is independent of PG. In the pregnant uteri, PG release was further markedly enhanced by OT. The PG content, however, was not significantly altered. Thus, our findings support the hypothesis that the marked increase in sensitivity of the parturient uterus to OT is related to an enhanced PG synthesis and release induced by OT. The possibility that the uterotonic and PG-releasing actions of OT are two separate functions of OT, each acting on a different receptor site and/or mechanism is discussed.