Tanabe N, Ueno A, Tsujimoto G
Department of Urology, Yamanashi Medical College, Japan.
J Urol. 1993 Sep;150(3):1056-9. doi: 10.1016/s0022-5347(17)35685-9.
Angiotensin II (Ang II) receptors in the rat urinary bladder smooth muscle were investigated by in vitro responses of smooth muscle strips to exogenous Ang II stimulation and in radioligand binding assays. Ang II (10(-10) M. to 10(-5) M.) caused a potent contractile response in a concentration-dependent manner. Using the recently developed nonpeptide subtype-selective antagonists, the Ang II-induced contractile response was further characterized. The Ang II-induced contractile response was inhibited weakly by the type 2 subtype (AT2)-selective antagonist PD123319 but was potently inhibited by the type 1 subtype (AT1)-selective antagonist DuP 753 with a pA2 value of 9.03, suggesting that the response is mediated predominantly by AT1 receptors. [125I]Ang II was used to specifically label a single class of binding sites with a dissociation constant of 0.31 nM. and a maximal binding capacity of 41.5 fmol./mg. of protein. DuP 753 could completely antagonize the binding of Ang II in a particulate fraction of rat bladder (Ki = 14 nM), whereas PD123319 did not have any effect in the concentration range of 10(-9) to 10(-5) M. The results suggest that AT1 receptors rather than AT2 receptors predominantly mediate Ang II-induced contraction in the rat urinary bladder.
通过膀胱平滑肌条对外源性血管紧张素II（Ang II）刺激的体外反应以及放射性配体结合试验，对大鼠膀胱平滑肌中的Ang II受体进行了研究。Ang II（10^(-10) M至10^(-5) M）以浓度依赖性方式引起强烈的收缩反应。使用最近开发的非肽类亚型选择性拮抗剂，对Ang II诱导的收缩反应进行了进一步表征。Ang II诱导的收缩反应被2型亚型（AT2）选择性拮抗剂PD123319轻度抑制，但被1型亚型（AT1）选择性拮抗剂DuP 753有效抑制，pA2值为9.03，表明该反应主要由AT1受体介导。[125I]Ang II用于特异性标记一类结合位点，其解离常数为0.31 nM，最大结合容量为41.5 fmol/mg蛋白质。DuP 753可完全拮抗大鼠膀胱颗粒部分中Ang II的结合（Ki = 14 nM），而PD123319在10^(-9)至10^(-5) M的浓度范围内没有任何作用。结果表明，在大鼠膀胱中，AT1受体而非AT2受体主要介导Ang II诱导的收缩。
