Prostaglandins modulate hormonal effects on rabbit myometrial alpha 1-adrenergic responses.
Estrogen increases the alpha 1-adrenergic contractile sensitivity of the rabbit uterus. Since estrogen treatment increases prostaglandin (PG) production by the perfused rabbit uterus, and PGs contribute to the alpha 1-adrenergic contractile response, we postulated that estrogen's effects on PG production or response may play a role in the increased alpha 1-adrenergic sensitivity induced by estrogen. We studied the effects of the eicosanoid synthesis inhibitor meclofenamate (60 microM) on the response to epinephrine (10(-9)-10(-5) M) of uterine strips from ovariectomized, mature, and estrogen-treated rabbits in terms of both contractile response and PGE2 and PGF2 alpha production. We also measured the contractile response to PGE2 and PGF2 alpha (both 10(-10)-10(-5) M) and KCl (70 mM) of uterine strips from these groups. We found that in the ovariectomized rabbits, meclofenamate decreased PG production, but did not alter the alpha 1-adrenergic sensitivity. In the mature rabbit uterus, meclofenamate decreased both PGE2 and PGF2 alpha production and reduced the alpha 1-adrenergic sensitivity. In the estrogen-treated rabbit uterus, meclofenamate decreased PGF2 alpha, but not PGE2, production and did not alter the alpha 1-adrenergic sensitivity. Finally, meclofenamate reduced the contractile response to KCl in all three groups, and exposure to PGE2 increased the contractile response to KCl in both the mature and estrogen-treated rabbits. We conclude that PGs play a role in the increase in the alpha 1-adrenergic sensitivity of the uterus in mature rabbits, and that this may be the result of an estrogen-mediated alteration in the postreceptor effects of PGs.
Hurd
W W
WW
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco 94143.
Riemer
R K
RK
Goldfien
A
A
Roberts
J M
JM
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008469:Meclofenamic Acid / Q000494:pharmacology*; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D011433:Propranolol / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis / Q000378:metabolism*; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects*
D011453:Prostaglandins; D011942:Receptors, Adrenergic, alpha; D008469:Meclofenamic Acid; D004958:Estradiol; D011433:Propranolol; D015237:Dinoprost; D003042:Cocaine; D015232:Dinoprostone; D004837:Epinephrine