Effect of estrogen on intracellular signaling pathways linked to activation of M(2)- and M(3)-muscarinic acetylcholine receptors in the rat myometrium.

The estrogen treatment of adult female rats induces an increase in myometrium sensitivity to cholinergic agonists and in this tissue the presence of M(2)- and M(3)-muscarinic acetylcholine (mACh) receptor was shown. We now report the effect of estrogen on intracellular signaling pathways linked to activation of M(2)- and M(3)-mACh receptor subtypes. The intracellular cyclic AMP accumulation and [3H]-inositol phosphates content were measured in myometrium strips from rats in estrus (control) and estradiol-treated rats (12.5 microg/100 g body weight, sc, 24 h before experiments) (the plasma estradiol level was 30.9+/-3.5 pg/ml and 119.3+/-14.1 pg/ml from control and estrogen-treated rats, respectively). Estrogen treatment increased 2.5-fold the intracellular cyclic AMP accumulation induced by 10 microM forskolin. The effects of muscarinic agonist and antagonists on cyclic AMP accumulation were tested. Carbachol reduced the forskolin-induced intracellular cyclic AMP content, 3.0 and 10.5-fold, in myometrium from control and estradiol-treated rats, respectively. This inhibitory effect failed to occur when carbachol was incubated in the presence of methoctramine. Carbachol also induced increase on total [3H]-inositol phosphates accumulation in myometrium from estradiol-treated rats when compared with control rats. This effect was reversed by pfHHSiD. These studies suggest the modulation by estrogen of intracellular signaling pathways linked to activation of M(2)- and M(3)-mACh receptors in the rat myometrium.