title: Effects of inhibition of prostaglandin synthesis on uterine oxytocin receptor concentration and myometrial gap junction density in parturient rats.
abstract: The development of oxytocin (OT) sensitivity in the parturient uterus is associated with increases in myometrial OT receptor concentration, gap junction formation, and prostaglandin (PG) production. To investigate whether PGs mediate these responses, we measured OT responsiveness, OT receptor concentrations, and gap junction formations in uteri of Day 19, 20, 21, 22, 23 pregnant and Day 2 postpartum rats. Inhibition of endogenous PG synthesis was produced by infusion of naproxen sodium delivered by an implanted osmotic pump. Naproxen treatment, but not placebo treatment, markedly attenuated in vitro uterine PGE2, PGF2 alpha, and PGI2 releases, suppressed OT responsiveness, and prolonged gestation. The increase of OT receptor concentration that normally occurred on Day 23 term pregnancy was delayed to Day 24. Co-administration of PGF2 alpha reversed the suppressive effects of naproxen. Naproxen treatment did not significantly affect gap junction formations on Day 23 but appeared to delay both the onset and disappearance of gap junction formations. PGF2 alpha co-administration with naproxen also had no apparent effect on gap junction development. The inhibition of OT receptor formation but not gap junction formation on Day 23 in the presence of naproxen indicates that these two events are controlled independently. Furthermore, the failure of naproxen-treated rats to deliver at term suggests that gap junction formation in the absence of an increase in OT receptors is insufficient to initiate labor. It appears that increases in both OT receptor concentrations and gap junction densities may be required for labor.
authors.affiliation: Department of Pharmacology, Cornell University Medical College, New York, New York 10021.
authors.forename: W Y
authors.initials: WY
authors.lastname: Chan
authors.forename: I
authors.initials: I
authors.lastname: Berezin
authors.forename: E E
authors.initials: EE
authors.lastname: Daniel
mesh_terms: D000818:Animals; D005260:Female; D007365:Intercellular Junctions / Q000502:physiology*; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009288:Naproxen / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism / Q000502:physiology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000502:physiology*; D018045:Receptors, Oxytocin
chemical_list: D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; D009288:Naproxen