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 β3-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.
Highlights
Background and aimsThe incidence of premature birth has risen over the past 15 years, mainly because of medically induced births, yet spontaneous preterm delivery rate continues its steady rise and remains relatively high in developed countries, despite preventative measures [1,2,3]
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
Using an RT-PCR approach we found that mRNA expression was detected, as an expected 650 bp fragment, in human myometrium (Figure 3)
Summary
The incidence of premature birth has risen over the past 15 years, mainly because of medically induced births, yet spontaneous preterm delivery rate continues its steady rise and remains relatively high in developed countries, despite preventative measures [1,2,3]. Several stimulatory and inhibitory pathways regulate the balance of uterine quiescence and contractile activity during pregnancy, but the specific changes that govern the switch between these opposing functional states are still poorly understood These data explain that a logical research pursuit has been that of development of pharmacological agents that inhibit uterine contractions and ideally terminate the labor process, or delay delivery until gestation is further advanced. ADRB2 [20,21,22,23] and the presence of ADRB3 had never been studied prior to our investigations presented here These works aimed to assess the presence and function of ADRB3 in human myometrium and to assess the influence of pregnancy in its expression as well as its ability to resist to agonist-induced desensitization
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