title: Is the beta3-adrenoceptor (ADRB3) a potential target for uterorelaxant drugs?
abstract: The management of premature birth still remains unsatisfactory. Since the relative lack of efficiency and/or safety of current tocolytic agents have been highlighted, it is necessary to develop new uterorelaxant drugs deprived of important maternal and foetal side effects. Our work reported in this review focuses on a potential new target for tocolytic drugs, the beta3-adrenoceptor (ADRB3). This third type of ADRB is shown to be present and functional in human myometrium. We demonstrated that ADRB3 agonists are able to inhibit in-vitro spontaneous contractions of myometrial strips, via a cyclic AMP-mediated pathway. Furthermore, we established that ADRB3 is the predominant subtype over the ADRB2 in human myometrium and that its expression is increased in near-term myometrium, compared to non-pregnant myometrium. Finally, we reported that contrary to ADRB2, the human myometrial ADRB3 is resistant to long-term agonist-induced desensitisation. These compelling data confirm the clinical potential interest of ADRB3 agonists in the pharmacological management of preterm labour.
authors.affiliation: Laboratoire de Physiologie et Pharmacologie Cardiovasculaires Expérimentales, Faculté de Médecine, Université de Bourgogne, Dijon Cedex, France. marc.bardou@u-bourgogne.fr
authors.forename: Marc
authors.initials: M
authors.lastname: Bardou
authors.forename: Céline
authors.initials: C
authors.lastname: Rouget
authors.forename: Michèle
authors.initials: M
authors.lastname: Breuiller-Fouché
authors.forename: Catherine
authors.initials: C
authors.lastname: Loustalot
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Naline
authors.forename: Paul
authors.initials: P
authors.lastname: Sagot
authors.forename: René
authors.initials: R
authors.lastname: Frydman
authors.forename: Esteban J
authors.initials: EJ
authors.lastname: Morcillo
authors.forename: Charles
authors.initials: C
authors.lastname: Advenier
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Leroy
authors.forename: John J
authors.initials: JJ
authors.lastname: Morrison
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects*; D007752:Obstetric Labor, Premature / Q000188:drug therapy* / Q000517:prevention & control; D011247:Pregnancy; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000378:metabolism
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D022702:Receptors, Adrenergic, beta-3