Characteristics of the alpha 2/beta 2-adrenergic receptor-coupled adenylyl cyclase system in rat myometrium during pregnancy.

alpha 2A- and alpha 2B-adrenoreceptors (AR), identified by Northern blotting in rat myometrium, showed a differential expression during the course of pregnancy. Indeed, the alpha 2A-AR transcript was present at mid-pregnancy, whereas high levels of alpha 2B-AR mRNA could be detected at term. The role of these subtypes in modulating beta 2-AR-stimulated adenylyl cyclase activity was investigated on myometrial membranes from mid-pregnancy and term. At nanomolar concentrations of clonidine (full alpha 2-AR agonist) or oxymetazoline (partial alpha 2A-AR agonist), adenylyl cyclase activity was inhibited by up to 50 +/- 7% at mid-pregnancy or 75 +/- 7% at term, whereas at micromolar concentrations, alpha 2-AR agonists potentiate adenylyl cyclase activity by 140-170% at mid-pregnancy. Both inhibitory and stimulatory components of this biphasic response were blocked by yohimbine, a selective alpha 2-AR antagonist. Preincubation of myometrial membranes with Gi2 and/or Gi3 antisera eliminated alpha 2-AR mediated attenuation or potentiation of isoproterenol-stimulated adenylyl cyclase, thus indicating that both the inhibitory and stimulatory components are mediated via Gi2 and Gi3. In addition, type II and IV adenylyl cyclases were identified by Northern blotting in the pregnant rat myometrium. Altogether these data strongly suggest that the alpha 2A-AR at mid-pregnancy potentiates adenylyl cyclase types II and IV through beta gamma released from Gi2 and Gi3 proteins, whereas the alpha 2B-AR expression at term may be related to persistent inhibition.