Is the beta3-adrenoceptor (ADRB3) a potential target for uterorelaxant drugs?
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.
Bardou
Marc
M
Laboratoire de Physiologie et Pharmacologie Cardiovasculaires Expérimentales, Faculté de Médecine, Université de Bourgogne, Dijon Cedex, France. marc.bardou@u-bourgogne.fr
Rouget
Céline
C
Breuiller-Fouché
Michèle
M
Loustalot
Catherine
C
Naline
Emmanuel
E
Sagot
Paul
P
Frydman
René
R
Morcillo
Esteban J
EJ
Advenier
Charles
C
Leroy
Marie-Josèphe
MJ
Morrison
John J
JJ
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
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D022702:Receptors, Adrenergic, beta-3