β-Adrenergic-receptor and adenylate cyclase properties in pregnant and nonpregnant guinea pig myometrium

Abstract

Stimulation of myometrial β-adrenergic receptors by agonists results in myometrial relaxation through adenylate cyclase-dependent mechanisms. Their activity is modulated by local or systemic estrogen-progesterone milieu. During pregnancy, guinea pigs demonstrate an ovarioplacental shift for progesterone production at ⩽0.35 gestation and a gradual increase in estrogen levels. To investigate whether these changes affect myometrial β-adrenergic-receptor and adenylate cyclase properties, we directly characterized β-adrenergic receptors and adenylate cyclase in myometrial plasma membranes from time-dated pregnant (term 65 days), postpartum, and nonpregnant virgin guinea pigs by well-established in vitro methods. In all animals, there appeared to be a high-affinity, low-capacity, single class of binding sites with pharmacologic specificities consistent with the β2-adrenergic-receptor subtype. The dissociation constants of these β-adrenergic receptors were significantly decreased in pregnant animals at approximately ⩾0.80 gestation when compared to pregnant animals at 0.35 to 0.40 gestation, nonpregnant animals, and postpartum animals. Moreover, the total number of β-adrenergic receptors was significantly higher at ⩾0.80 gestation than in the other groups. Basal adenylate cyclase activity increased in animals from 0.35 to ⩾0.8 gestation and was higher than that of postpartum animals and nonpregnant animals. The degree of adenylate cyclase stimulation by (−)isoproterenol was higher at term than at an earlier point in gestation or in nonpregnant and postpartum animals. These results indicate that, with advancing gestation in pregnant animals, there is an up-regulation of β-adrenergic-receptor and adenylate cyclase function.