Pharmacology, Research and Development, Kissei Pharmaceutical Co. Ltd., 4365-1, Kashiwabara, Hotaka, Azumino, Nagano 399-8304, Japan.
World J Urol. 2009 Dec;27(6):775-80. doi: 10.1007/s00345-009-0396-y.
This study was performed to characterize the α1-adrenoceptor subtypes in mouse ureters as regards gene expressions and contractile functions.
The mRNAs for these subtypes were quantified by the real-time quantitative reverse transcription polymerase chain reaction. In a functional study, α1-adrenoceptor antagonists were evaluated against the noradrenaline-induced contraction in mouse isolated ureteral preparations.
In mouse ureter, the relative mRNA expression levels for α1a-, α1b- and α1d-adrenoceptors were 74.5, 14.3 and 11.2%, respectively. Adrenaline and noradrenaline each produced a concentration-dependent phasic contraction (pD 2 values, 5.73±0.05 and 5.69±0.06, respectively). Prazosin (non-selective α1-adrenoceptor antagonist), silodosin (selective α1A-adrenoceptor antagonist), and BMY-7378 (selective α1D-adrenoceptor antagonist) all shifted the concentration–response curve for noradrenaline to the right, the rank order of potencies (apparent pA 2 values) being silodosin (9.32±0.11)>prazosin (8.55±0.10)>BMY-7378 (6.06±0.15). The α1A-adrenoceptor antagonist silodosin was thus much more effective than the α1D-adrenoceptor antagonist BYM-7378.
Our results demonstrate that in mouse ureters: the mRNA for the α1A-adrenoceptor was more prevalent than those for the α1B- and α1D-adrenoceptors, and that among these subtypes, the α1A-adrenoceptor plays the major role in noradrenaline-induced contraction.
本研究旨在对小鼠输尿管中的α1-肾上腺素受体亚型进行基因表达和收缩功能分析。
采用实时定量逆转录聚合酶链反应测定这些亚型的 mRNA。在功能研究中，评估了α1-肾上腺素受体拮抗剂对小鼠离体输尿管标本中去甲肾上腺素诱导收缩的作用。
在小鼠输尿管中，α1a-、α1b-和α1d-肾上腺素受体的相对 mRNA 表达水平分别为 74.5%、14.3%和 11.2%。肾上腺素和去甲肾上腺素均产生浓度依赖性的相位收缩（pD2 值分别为 5.73±0.05 和 5.69±0.06）。哌唑嗪（非选择性α1-肾上腺素受体拮抗剂）、西洛多辛（选择性α1A-肾上腺素受体拮抗剂）和 BMY-7378（选择性α1D-肾上腺素受体拮抗剂）均使去甲肾上腺素的浓度-反应曲线右移，效价顺序（表观 pA2 值）为西洛多辛（9.32±0.11）>哌唑嗪（8.55±0.10）>BMY-7378（6.06±0.15）。因此，α1A-肾上腺素受体拮抗剂西洛多辛比α1D-肾上腺素受体拮抗剂 BMY-7378更有效。
我们的结果表明，在小鼠输尿管中：α1A-肾上腺素受体的 mRNA 比α1B-和α1D-肾上腺素受体更丰富，而在这些亚型中，α1A-肾上腺素受体在去甲肾上腺素诱导的收缩中起主要作用。
