title: The alpha1B-adrenergic receptor subtype activates the phospholipase C signaling pathway in rat myometrium at parturition.
abstract: This study demonstrates that alpha1-adrenergic receptors previously identified in the pregnant rat myometrium are heterogeneous. They can be subtyped alpha1A- and alpha1B-adrenergic receptors on the basis of their affinity for the antagonists WB4101 (alpha1A > alpha1B) and chloroethylclonidine (alpha1B selective). Between Day 21 of pregnancy and term, the proportion of [3H]prazosin binding sites with low affinity for WB4101 and sensitive to inactivation by 10(-5) M chloroethylclonidine under hypotonic conditions (alpha1B subtype) remained constant. In contrast, the number of [3H]prazosin binding sites with a high affinity for WB4101 and insensitive to chloroethylclonidine (alpha1A subtype) increased by 88% at term. The effect of 5'-guanylylimidodiphosphate (Gpp[NH]p) on competition of the agonist phenylephrine for [3H]prazosin binding in the presence of WB4101 or after chloroethylclonidine pretreatment indicates that the alpha1A-adrenergic receptor underwent uncoupling whereas the alpha1B-adrenergic receptor-G protein coupled state was increased (+ 63%). Phenylephrine consistently stimulated phospholipase C activity on membrane fractions prepared from term myometria. This stimulation was completely inhibited after 10(-5) M chloroethylclonidine but was not consistently decreased with 5-methylurapidyl, a selective alpha1A-antagonist. Furthermore QL antibody (anti-G alpha(q)/G alpha11) also specifically blocked the phenylephrine-stimulated phospholipase C activity. Altogether these results strongly suggest that activation of the alpha1B-adrenergic receptor subtype in the pregnant myometrium at term may contribute to the stimulation of the G alpha(q)/G alpha11/phospholipase C signaling pathway.
authors.affiliation: Laboratoire de Physiologie de la Reproduction, CNRS URA 1449, Université Pierre et Marie Curie, Paris, France. jean-paul.maltier@snv.jussieu.fr
authors.forename: I
authors.initials: I
authors.lastname: Limon-Boulez
authors.forename: S
authors.initials: S
authors.lastname: Mhaouty-Kodja
authors.forename: N
authors.initials: N
authors.lastname: Coudouel
authors.forename: A
authors.initials: A
authors.lastname: Benoit de Coignac
authors.forename: C
authors.initials: C
authors.lastname: Legrand
authors.forename: J P
authors.initials: JP
authors.lastname: Maltier
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics; D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007743:Labor, Obstetric / Q000502:physiology*; D009215:Myometrium / Q000294:innervation / Q000502:physiology*; D011247:Pregnancy; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D018342:Receptors, Adrenergic, beta-1; D006165:Guanylyl Imidodiphosphate; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D010738:Type C Phospholipases; D003000:Clonidine