In vivo stimulation of the beta(2)-adrenergic pathway increases expression of the Gi proteins and the alpha(2)A-adrenergic receptor genes in the pregnant rat myometrium.
Cross-regulations between Gs and Gi mediated pathways controlling the adenylyl cyclase activity have been clearly demonstrated in vitro. To elucidate whether activation of the beta-adrenergic pathway in the pregnant myometrium might affect Gi proteins and alpha(2)-adrenergic receptors (ARs), we treated late pregnant rats from day 18 to day 21 with twice-daily administration of isoproterenol (8 mg/kg). This treatment increased myometrial cAMP levels and led after 76 h to a significant and maximal rise in the immunoreactive amount of myometrial Gi alpha 2 and Gi alpha 3 proteins (1.4- and 1.7-fold respectively) associated with a parallel increase of the steady-state levels of both Gi alpha 2 and Gi alpha 3 mRNA (1.6- and 1.9-fold respectively). Propranolol antagonized this response indicating the implication of the beta-adrenergic pathway. Nuclear run-on assays demonstrated that isoproterenol enhanced respectively by 1.3- and 1.2-fold the transcription rate of the Gi alpha 2 and Gi alpha 3 genes. Quantification of myometrial alpha(2)-ARs by [3H]rauwolscine binding revealed that the total number of receptors was also increased at 76 h by 1.7-fold when compared with controls, with no change in the affinity of the alpha(2)-ARs for the ligand. This effect was antagonized by propranolol. Quantification of both alpha(2A)- and alpha(2B)-subtypes by Northern blotting analysis demonstrated that this elevation was due to a selective increase of the alpha(2A)-subtype mRNAs. The present results indicate that in vivo stimulation of the beta-adrenergic pathway by isoproterenol increases both Gi alpha 2/Gi alpha 3 and alpha(2A)-AR expression in the pregnant rat myometrium. The possible contribution of such a mechanism in pregnancy-related changes of both entities is discussed.
Lécrivain
J L
JL
Laboratoire de Physiologie de la Reproduction, CNRS URA 1449, Université P.M. Curie, Paris, France.
Mhaouty-Kodja
S
S
Cohen-Tannoudji
J
J
Maltier
J P
JP
Legrand
C
C
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D015151:Immunoblotting; D007545:Isoproterenol / Q000494:pharmacology*; D009215:Myometrium / Q000378:metabolism*; D011247:Pregnancy; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D011433:Propranolol; D000242:Cyclic AMP; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007545:Isoproterenol