Beta3-adrenoceptor is the predominant beta-adrenoceptor subtype in human myometrium and its expression is up-regulated in pregnancy.
To assess whether pregnancy might influence the functionality and expression of human myometrial beta(2)- and beta(3)-adrenoceptors (beta(2)- and beta(3)-AR), we performed functional, binding, Western blot, and molecular biology experiments in human nonpregnant and near-term pregnant myometrium. Inhibition of spontaneous contractions induced by a beta(3)-AR agonist, SR 59119A, was significantly greater in pregnant, compared with nonpregnant, myometrial strips (E'(max) = 61 +/- 5% vs. 44 +/- 5% for pregnant and nonpregnant myometrium, respectively), whereas salbutamol, a beta(2)-AR agonist, was significantly less efficient in pregnant, compared with nonpregnant, myometrium (E(max) = 29 +/- 4 vs. 54 +/- 8%). Although two populations of binding sites corresponding to beta(2)- and beta(3)-AR were identified in both nonpregnant and pregnant myometrium, we found a clear predominance of the beta(3)-AR subtype. Moreover, beta(3)-AR binding sites were up-regulated 2-fold in myometrium at the end of pregnancy. Both beta(2)- and beta(3)-AR mRNA were expressed in human nonpregnant and pregnant myometrium. Contrary to beta(2)-AR, the expression of the beta(3)-AR transcripts and immunoreactive proteins was increased in pregnant, compared with nonpregnant, myometrium. Such compelling data suggest a predominant role for beta(3)-AR in the regulation of human myometrium contractility, especially at the end of pregnancy, which might have important consequences for the clinical management of preterm labor.
Rouget
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Unité Propre de Recherche de l'Enseignement Supérieur EA220-Pharmacology, Unité de Formation et de Recherche Biomédicale des Saints Pères, 45 rue des Saints Pères, F-75006 Paris, France. celine.rouget@univ-paris5.fr
Bardou
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Breuiller-Fouché
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Loustalot
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Qi
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Naline
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Croci
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Cabrol
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Advenier
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Leroy
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D001665:Binding Sites / Q000502:physiology; D015153:Blotting, Western; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D009215:Myometrium / Q000502:physiology*; D011247:Pregnancy / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics* / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; C114930:SR 59119A; D013764:Tetrahydronaphthalenes; D000420:Albuterol