Endocrinology, Vol 111, 48-54, Copyright © 1982 by Endocrine Society

ARTICLES

Antioxytocic and antiprostaglandin-releasing effects of oxytocin antagonists in pregnant rats and pregnant human myometrial strips

WY Chan, AM Powell and VJ Hruby

There is now increasing evidence that both oxytocin (OT) and prostaglandin (PG) play a role in term as well as preterm labor. OT stimulates myometrial contractions and uterine PG release. Specific OT antagonists, therefore, may be of value in the treatment of preterm labor. Recently, we have synthesized two highly potent OT antagonists, [1-penicillamine, 4-threonine]OT ([Pen1, Thr4]OT) and [1-penicillamine, 2-phenylalanine, 4-threonine]OT ([Pen1, Phe2, Thr4]OT). We have determined their antioxytocic activity in 21- to 22-day-pregnant rats and on isolated human myometrial strips obtained from term pregnant patients at caesarean section for childbirth. We also studied their effects on PG synthesis and OT-stimulated PG synthesis on uterine slices from pregnant rats. We found that the two OT antagonists were effective inhibitors of the OT responses in pregnant rats and on pregnant human myometrial strips. The two OT antagonists had no agonistic activity on PG release at a dose range that was antioxytocic. When administered together with OT, the PG-releasing action of OT was inhibited. Thus, [Pen1, Thr4]OT and [Pen1, Phe2, Thr4]OT are effective inhibitors of both the uterotonic and PG-releasing actions of OT. The potentials of OT antagonists as tocolytic agents for the treatment of preterm labor should be explored.

This article has been cited by other articles:

				G. Weiss Endocrinology of Parturition J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4421 - 4425. [Full Text]

				C.A. Umscheid, W.X. Wu, P. Gordan, and P.W. Nathanielsz Up-Regulation of Oxytocin Receptor Messenger Ribonucleic Acid and Protein by Estradiol in the Cervix of Ovariectomized Rat Biol Reprod, November 1, 1998; 59(5): 1131 - 1138. [Abstract] [Full Text]