Moriyama N, Kurooka Y, Nasu K, Akiyama K, Takeuchi T, Nishimatsu H, Murata S, Murayama T, Tsujimoto G, Kawabe K
Department of Urology, Faculty of Medicine, The University of Tokyo, Japan.
Life Sci. 2000;66(10):915-26. doi: 10.1016/s0024-3205(99)00675-x.
This study was intended to quantify the amounts of the alpha1-adrenoceptor subtype mRNAs in human renal artery and to demonstrate the distribution of receptor subtypes responsible for the contraction of the renal artery. RNase protection assay showed that the mean amount of alpha1a mRNA was much greater than that of alpha1b or alpha1d mRNAs in both the main and branch renal arteries. However, the abundance of alpha1a mRNA in human renal artery was much less than in our previous data in the prostate. In situ hybridization showed that all alpha1 subtype mRNAs were localized in the smooth muscle cells of the tunica media of the artery, and the distribution pattern of these three mRNAs in the main artery was the same as in the branch artery. However, the intensity of signals for alpha1d and alpha1b antisense RNAs probes was lower than that for the alpha1a antisense RNA probe. In the functional study, concentration-response curves to noradrenaline pretreated with KMD-3213, an alpha1A/L-adrenoceptor selective antagonist, seemed to be biphasic in nature. Chloroethyclonidine (CEC) failed to inactivate the noradrenaline-induced contraction, and prazosin showed relatively low affinity with a pA2 value of 8.8. These data suggest that the alpha1A/L-adrenoceptor mediates primarily those responses to noradrenaline in this artery. The other alpha1-adrenoceptor subtypes could also mediate the secondary contractile response to noradrenaline in this artery.
本研究旨在定量检测人肾动脉中α1 - 肾上腺素能受体亚型mRNA的含量，并证明负责肾动脉收缩的受体亚型的分布。核糖核酸酶保护试验表明，在肾动脉主支和分支中，α1a mRNA的平均含量远高于α1b或α1d mRNA。然而，人肾动脉中α1a mRNA的丰度远低于我们之前在前列腺中的数据。原位杂交显示，所有α1亚型mRNA均定位于动脉中膜的平滑肌细胞，这三种mRNA在主动脉中的分布模式与分支动脉相同。然而，α1d和α1b反义RNA探针的信号强度低于α1a反义RNA探针。在功能研究中，用α1A/L - 肾上腺素能受体选择性拮抗剂KMD - 3213预处理后对去甲肾上腺素的浓度 - 反应曲线似乎呈双相性。氯乙可乐定（CEC）未能使去甲肾上腺素诱导的收缩失活，哌唑嗪显示出相对较低的亲和力，pA2值为8.8。这些数据表明，α1A/L - 肾上腺素能受体主要介导该动脉对去甲肾上腺素的那些反应。其他α1 - 肾上腺素能受体亚型也可介导该动脉对去甲肾上腺素的继发性收缩反应。
