Molecular and functional characteristics of ??3- adrenoceptors in late pregnant mouse uterus: A comparison with ??2-adrenoceptors

摘要

??3-adrenoceptor is a potential target for uterine relaxant drugs for the treatment of preterm labor. Mouse is an ideal experimental model for preterm labor. However, there is limited information on the molecular and functional characteristics of ??3-adrenoceptors in mouse uterus. Therefore, the current study was undertaken to characterize the ??3-adrenoceptors in late pregnant mouse uterus by molecular and functional experiments and to compare their expression and function with the ??2-adrenoceptors. Using RT-PCR, we demonstrated the presence of ??3-adrenoceptor mRNA in the mouse uterus. Accordingly, selective ??3-adrenoceptor agonist SAR150640 (ethyl-4-{trans-4-[((2S)-2- hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl)amino]cyclohexyl} benzoate hydrochloride) caused concentration-dependent relaxation of the isolated tissue. SR59230A (1 ??M), a selective antagonist of ??3-adrenoceptors, antagonized the relaxant response to SAR150640. Using real-time PCR we found that in comparison to ??3-adrenoceptor mRNA, ??2-adrenoceptor mRNA is predominantly expressed in the late pregnant mouse uterus. We then assessed the comparative efficiency of different ??-adrenoceptor agonists, such as SAR150640, salbutamol and isoprenaline to relax the tissue. SAR150640 (pD 2 6.64??0.21, Emax 104.9??7.95), salbutamol (pD2 8.57??0.062, Emax 103.1??3.22) and isoprenaline (pD2 9.48??0.084, Emax 102.9??5.18) caused concentration-dependent inhibition of uterine rhythmic contractions. While the maximal relaxation to these agonists was comparable, the order of potency was isoprenalinesalbutamolSAR. These results suggest that ??3-adrenoceptor mRNA is present in the pregnant mouse uterus and is functionally active. The predominance of ??2- over ??3-adrenoceptor expression may explain variable potency amongst the ??-adrenoceptor agonists. ? 2012 Elsevier B.V.