Pulmonary, gastrointestinal and urogenital pharmacologyMolecular and functional characteristics of β3-adrenoceptors in late pregnant mouse uterus: A comparison with β2-adrenoceptors

β3-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 β3-adrenoceptors in mouse uterus. Therefore, the current study was undertaken to characterize the β3-adrenoceptors in late pregnant mouse uterus by molecular and functional experiments and to compare their expression and function with the β2-adrenoceptors. Using RT-PCR, we demonstrated the presence of β3-adrenoceptor mRNA in the mouse uterus. Accordingly, selective β3-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 μM), a selective antagonist of β3-adrenoceptors, antagonized the relaxant response to SAR150640. Using real-time PCR we found that in comparison to β3-adrenoceptor mRNA, β2-adrenoceptor mRNA is predominantly expressed in the late pregnant mouse uterus. We then assessed the comparative efficiency of different β-adrenoceptor agonists, such as SAR150640, salbutamol and isoprenaline to relax the tissue. SAR150640 (pD2 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 isoprenaline>salbutamol>SAR. These results suggest that β3-adrenoceptor mRNA is present in the pregnant mouse uterus and is functionally active. The predominance of β2- over β3-adrenoceptor expression may explain variable potency amongst the β-adrenoceptor agonists.