Stimulation of ovine myometrial activity by 6-keto prostaglandin E1

6-keto prostaglandin E₁ (6KE) is a metabolite of PGI₂, which we have shown previously inhibits spontaneous myometrial activity. In the present study we examined the effects of 6KE on uterine electrical and mechanical activity in non-pregnant ovariectomized sheep. 6KE stimulated uterine activity in a dose-dependent fashion. The effect was enhanced by pre-treatment with estradiol (E2). It was not influenced by pre-treatment with meclofenamic acid and was not associated with significant changes in the concentrations of 13,14 dihydro 15-keto PGF_2α in vena cava plasma. After E2 treatment, 6KE had 0.2–0.3 of the stimulatory activity of PGF_2α. In the absence of E2, the uterine response to both 6KE and PGF_2α was decreased. In animals in which spontaneous myometrial activity was inhibited by PGI2, the uterus remained responsive to 6KE. We conclude that in the ovariectomized non-pregnant sheep 6KE stimulates uterine activity, and that the effect is independent of endogenous PG production.