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Characteristics of the α2/β2-Adrenergic Receptor-coupled Adenylyl Cyclase System in Rat Myometrium during Pregnancy

1995; Elsevier BV; Volume: 270; Issue: 18 Linguagem: Inglês

10.1074/jbc.270.18.11012

1083-351X

Sakina Mhaouty‐Kodja, Joëlle Cohen-Tannoudji, Rachel Bouet‐Alard, Isabelle Limon, Jean‐Paul Maltier, Chantal Legrand,

Neuropeptides and Animal Physiology

α2A−- and α2B-adrenoreceptors (AR), identified by Northern blotting in rat myometrium, showed a differential expression during the course of pregnancy. Indeed, the α2A−-AR transcript was present at mid-pregnancy, whereas high levels of α2B-AR mRNA could be detected at term. The role of these subtypes in modulating β2-AR-stimulated adenylyl cyclase activity was investigated on myometrial membranes from mid-pregnancy and term. At nanomolar concentrations of clonidine (full α2-AR agonist) or oxymetazoline (partial α2A−-AR agonist), adenylyl cyclase activity was inhibited by up to 50 ± 7% at mid-pregnancy or 75 ± 7% at term, whereas at micromolar concentrations, α2-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 α2-AR antagonist. Preincubation of myometrial membranes with Gi2 and/or Gi3 antisera eliminated α2-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 α2A−-AR at mid-pregnancy potentiates adenylyl cyclase types II and IV through βγ released from Gi2 and Gi3 proteins, whereas the α2B-AR expression at term may be related to persistent inhibition. α2A−- and α2B-adrenoreceptors (AR), identified by Northern blotting in rat myometrium, showed a differential expression during the course of pregnancy. Indeed, the α2A−-AR transcript was present at mid-pregnancy, whereas high levels of α2B-AR mRNA could be detected at term. The role of these subtypes in modulating β2-AR-stimulated adenylyl cyclase activity was investigated on myometrial membranes from mid-pregnancy and term. At nanomolar concentrations of clonidine (full α2-AR agonist) or oxymetazoline (partial α2A−-AR agonist), adenylyl cyclase activity was inhibited by up to 50 ± 7% at mid-pregnancy or 75 ± 7% at term, whereas at micromolar concentrations, α2-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 α2-AR antagonist. Preincubation of myometrial membranes with Gi2 and/or Gi3 antisera eliminated α2-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 α2A−-AR at mid-pregnancy potentiates adenylyl cyclase types II and IV through βγ released from Gi2 and Gi3 proteins, whereas the α2B-AR expression at term may be related to persistent inhibition.