[3H]rauwolscine binding to myometrial alpha 2-adrenoceptors in pregnant guinea pig.

Uterine sympathetic nerves can exert an excitatory influence in late pregnancy and during parturition. Neuronal norepinephrine release is increased at these times and a diminished alpha 2-adrenoceptor-mediated prejunctional inhibition could account for this. To assess whether an altered receptor population may contribute, [3H]rauwolscine was used to measure alpha 2-adrenoceptors in myometrial membranes at time intervals throughout pregnancy. High affinity [3H]rauwolscine binding [Kd = 11.4 +/- 1.5 nM (n = 42)] yielded linear Scatchard plots that in nonpregnant myometrium indicated a maximum binding density (Bmax) of 217 +/- 42.4 fmol/mg protein. alpha 2-Adrenoceptor density was increased twofold at midpregnancy (31 days) and thereafter fell sharply by up to 90% toward term (67 +/- 2 days). When uterine growth is accounted for and data are expressed in terms of total myometrial population (uncorrected for plasma membrane recovery), alpha 2-adrenoceptor number was eightfold (midpregnancy) and fourfold (term) greater than the nonpregnant value of 804 +/- 322.4 fmol/uterus. alpha 2-Adrenoceptors were also found to bind dopamine with high affinity [Ki = 3.66 +/- 0.45 microM (n = 3)]. These observations could indicate a pregnancy-related change in uterine sympathetic autoinhibitory capacity and, since alpha 2-adrenoceptors appear also to be located postjunctionally, explain in part reports of altered myometrial responsiveness to norepinephrine infusion and also the uterotonic actions of dopamine.