Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India.
Eur J Pharmacol. 2013 Jan 30;700(1-3):74-9. doi: 10.1016/j.ejphar.2012.11.048. Epub 2012 Dec 5.
β(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 β(3)-adrenoceptors in mouse uterus. Therefore, the current study was undertaken to characterize the β(3)-adrenoceptors in late pregnant mouse uterus by molecular and functional experiments and to compare their expression and function with the β(2)-adrenoceptors. Using RT-PCR, we demonstrated the presence of β(3)-adrenoceptor mRNA in the mouse uterus. Accordingly, selective β(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 μM), a selective antagonist of β(3)-adrenoceptors, antagonized the relaxant response to SAR150640. Using real-time PCR we found that in comparison to β(3)-adrenoceptor mRNA, β(2)-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 (pD(2) 6.64±0.21, E(max) 104.9±7.95), salbutamol (pD(2) 8.57±0.062, E(max) 103.1±3.22) and isoprenaline (pD(2) 9.48±0.084, E(max) 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 β(3)-adrenoceptor mRNA is present in the pregnant mouse uterus and is functionally active. The predominance of β(2)- over β(3)-adrenoceptor expression may explain variable potency amongst the β-adrenoceptor agonists.
β(3)-肾上腺素能受体是治疗早产的子宫松弛药物的潜在靶点。小鼠是早产研究的理想实验模型。然而，关于小鼠子宫中β(3)-肾上腺素能受体的分子和功能特征的信息有限。因此，本研究通过分子和功能实验对孕晚期小鼠子宫中的β(3)-肾上腺素能受体进行了表征，并比较了其与β(2)-肾上腺素能受体的表达和功能。通过 RT-PCR，我们证明了β(3)-肾上腺素能受体 mRNA 存在于小鼠子宫中。相应地，选择性β(3)-肾上腺素能受体激动剂 SAR150640(ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl)amino]cyclohexyl}benzoate hydrochloride)引起离体组织的浓度依赖性松弛。选择性β(3)-肾上腺素能受体拮抗剂 SR59230A(1 μM)拮抗 SAR150640 的松弛反应。通过实时 PCR，我们发现与β(3)-肾上腺素能受体 mRNA 相比，β(2)-肾上腺素能受体 mRNA 在孕晚期小鼠子宫中主要表达。然后，我们评估了不同β-肾上腺素能受体激动剂，如 SAR150640、沙丁胺醇和异丙肾上腺素，对组织松弛的比较效率。SAR150640(pD2 6.64±0.21，E(max)104.9±7.95)、沙丁胺醇(pD2 8.57±0.062，E(max)103.1±3.22)和异丙肾上腺素(pD2 9.48±0.084，E(max)102.9±5.18)引起子宫节律性收缩的浓度依赖性抑制。虽然这些激动剂的最大松弛作用相当，但效力顺序为异丙肾上腺素>沙丁胺醇>SAR。这些结果表明，β(3)-肾上腺素能受体 mRNA 存在于妊娠小鼠子宫中，具有功能活性。β(2)-肾上腺素能受体表达的优势超过β(3)-肾上腺素能受体可能解释了β-肾上腺素能受体激动剂之间的可变效力。
