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.