The effects of ovarian hormones on beta-adrenergic and muscarinic receptors in rat heart.
The in vitro and in vivo effects of estrogen and progesterone on muscarinic and beta-adrenergic receptors of cardiac tissue were studied in ovariectomized (OVX) rats. The binding assay for muscarinic receptors was performed under a nonequilibrium condition; whereas the binding assay for beta-adrenergic receptors, under an equilibrium condition. Estrogenic compounds and progesterone were found to have no effect on the binding of the radioligand, [3H]-dihydroalprenolol, to beta-adrenergic receptors in vitro. However, progestins but not estrogenic compounds inhibited the binding of the radioligand, [3H]-quinuclidinyl benzilate, to muscarinic receptors in vitro, with progesterone as the most potent inhibitor (IC50 = 37 microM, apparent Ki = 13 microM). Progesterone was found to decrease the apparent affinity of muscarinic receptors for [3H](-)QNB in vitro. Daily treatment of OVX rats with estradiol benzoate (4 micrograms) or progesterone (2.5 mg) for 4 days had no effect on the muscarinic or beta-adrenergic receptors with respect to the binding affinity and receptor density. However, administrations of these hormones together for 4 days caused an increase in the receptor density of muscarinic receptors without a significant effect on their apparent binding affinity; also these hormones induced a decrease in the binding affinity and an increase in the receptor density of beta-adrenergic receptors. The results of this study demonstrate that progestins are capable of interacting with the cardiac muscarinic receptors in vitro, and indicate that estrogen and progesterone have a synergistic effect to increase the receptor densities of muscarinic and beta-adrenergic receptors as well as to cause a decrease in the binding affinity of beta-adrenergic receptors in vivo.
Klangkalya
B
B
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
Chan
A
A
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004082:Dihydroalprenolol / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D009206:Myocardium / Q000378:metabolism*; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D004967:Estrogens; D011372:Progestins; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D011374:Progesterone; D004958:Estradiol; D004082:Dihydroalprenolol; D011813:Quinuclidinyl Benzilate; D001285:Atropine