A quantitative analysis of mRNA expression of α1 and β-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders
A quantitative analysis of mRNA expression of α1 and β-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders
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DOI：
10.1097/01.ju.0000067621.62736.7c
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发表时间：
2003-08-01
影响因子：
6.6
通讯作者：
Yamaguchi, O
中科院分区：
文献类型：
--
作者：
Nomiya, M;Yamaguchi, O
目的：比较正常和梗阻人膀胱组织中α1肾上腺素受体(Alpha1-adrenoceptor，AR)亚型和β-AR亚型mRNA的表达水平，探讨膀胱出口梗阻对人逼尿肌α1-AR介导的收缩和β-AR介导的舒缩作用的影响。材料与方法：采用实时定量逆转录-聚合酶链式反应(RT-PCR)方法，定量检测α1和β-AR亚型mRNA的表达。结果：在对照组和梗阻组，α1a、α1b、α1d、β1和β2-AR mRNAs的mRNA表达水平较低，而β3-AR的表达水平最高。α1和β-AR亚型mRNA的表达水平在两组间差异无统计学意义。对照组和梗阻组对10(-4)M苯肾上腺素+/-扫描电子显微镜的平均收缩反应分别为10(-7)M卡巴胆碱引起的收缩的4.4%±1.4%和5.2%±1.4%。梗阻性膀胱对苯肾上腺素的收缩反应没有明显增加。异丙肾上腺素和β3-AR选择性激动剂L755,507以浓度依赖的方式(10(-9)~10(-4)M)松弛人逼尿肌。然而，β1/β2-AR激动剂多巴酚丁胺和β2-AR选择性激动剂克伦特罗在10(-9)~10(-5)M的浓度范围内均不产生松弛作用。结论：在人梗阻膀胱中，既没有α1-AR的上调，也没有β-AR的下调，介导β3-AR的松弛到目前为止仍占优势。因此，良性前列腺梗阻患者的逼尿肌过度活动和存储症状不太可能是由膀胱α-AR引起的。
Purpose: We compared the expression level of alpha1-adrenoceptor (AR) subtype mRNA to that of beta-AR subtype mRNA in control and obstructed human bladders, and examined whether alpha1-AR mediated contraction and beta-AR mediated relaxation of human detrusor muscle are altered by bladder outlet obstruction.Materials and Methods: A real-time quantitative reverse transcriptase-polymerase chain reaction based method was used to quantify alpha1 and beta-AR subtype mRNA expression. The contractile response to alpha-AR agonists and the relaxant effect of beta-AR agonists were examined using an isometric contraction technique.Results: The mRNA of alpha1a, alpha1b, alpha1d, beta1 and beta2-AR mRNAs was expressed at low levels, while beta3-AR was the most highly expressed subtype at the mRNA level in control and obstructed bladders. The expression level of alpha1 and beta-AR subtype mRNA was not significantly different between the 2 groups. The mean contractile response to 10(-4) M phenylephrine +/- SEM was only 4.4% +/- 1.4% and 5.2% +/- 1.4% of the 10(-7) M carbachol induced contraction in the control and obstructed groups, respectively. Contractile responses to phenylephrine were not significantly increased in obstructed bladder. Isoproterenol and the beta3-AR selective agonist L755,507 relaxed human detrusor muscle in a concentration dependent manner (10(-9) to 10(-4) M). However, the beta1/beta2-AR agonist dobutamine and the beta2-AR selective agonist clenbuterol did not produce relaxation at a concentration of 10(-9) to 10(-5) M in the 2 groups.Conclusions: These findings indicate that neither up-regulation of alpha1-ARs nor down-regulation of beta-ARs occurs and relaxation mediating beta3-ARs are by far predominant in the human obstructed bladder. Therefore, it is not likely that bladder alpha1-ARs are responsible for detrusor overactivity and storage symptoms in patients with benign prostatic obstruction.