Distribution and aging changes of αィイD21ィエD2-adrenoceptor subtype mRNA in human renal artery.

人肾动脉中αD21D2-肾上腺素受体亚型mRNA的分布和老化变化。

• 批准号: 10671459
• 负责人: MORIYAMA Nobuo
• 金额: $ 2.05万
• 依托单位: UNIVERSITY of TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671459/
• 关键词: Human renal artery; αィイD21ィエD2-adrenoceptor; αィイD21ィエD2-adrenoceptor mRNA; in situ hybridization; RNAase protection assay; ヒト腎実質

This study was intended to quantify the amounts of the αィイD21ィエD2-adrenoceptor subtype mRNAs in human renal artery, and demonstrate the distribution of receptor subtype responsible for the contraction of renal artery. RNase protection assay showed that the mean amount of αィイD21aィエD2-mRNA was much more than that of αィイD21bィエD2- or αィイD21dィエD2-mRNAs in both the main and branch renal arteries. However, the abundance of αィイD21aィエD2-mRNA in human renal artery was much less than our previous data in the prostate. By in situ hybridization, all αィイD21ィエD2 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 αィイD21dィエD2 and αィイD21bィエD2 antisense RNAs probes were lower than that for αィイD21aィエD2 antisense RNA probe. In the functional study, concentration-response curves to noradrenaline pretreated with KMD-3213, an αィイD21A/LィエD2-adrenoceptor selective antagonist, seemed to be biphasic curves. Chloroethyclonidine (CEC) failed to inactivate the noradrenaline-induced contraction and prazosin showed relatively low affinity with a pAィイD22ィエD2 value of 8.8. These data suggest that the αィイD21A/LィエD2-adrenoceptor primarily mediates those responses to noradrenaline in this artery. The other αィイD21ィエD2-adrenoceptor subtypes could also mediate the secondary contractile response to noradrenaline in this artery.

本研究旨在定量测定人肾动脉中α-肾上腺素D21受体D2-肾上腺素受体亚型mRNA的含量，并揭示肾动脉收缩的受体亚型分布。RNA酶保护实验显示，在肾主动脉和分支动脉中，α-淀粉样蛋白D21 a-D2-mRNA的平均表达量明显高于α-淀粉样蛋白D21 b-D2-或α-淀粉样蛋白D21 d-D2-mRNA。然而，人肾动脉中的α-β-D21 α-D2-mRNA的丰度远低于我们以前在前列腺中的数据。原位杂交结果显示，α-SMA D21亚型mRNA均定位于动脉图尼卡中膜平滑肌细胞，其在主动脉和分支动脉中的分布模式相同。而α α β D21 d β D2和α β D21 b β D2反义RNA探针的信号强度低于α β D21 a β D2反义RNA探针。在功能研究中，去甲肾上腺素经α-肾上腺素D21 A/L受体D2-受体选择性拮抗剂KMD-3213预处理后的量效曲线似为双相曲线。氯乙环尼定（CEC）未能抑制去甲肾上腺素诱导的收缩，哌唑嗪表现出相对较低的亲和力，其PA受体D22受体D2值为8.8。这些数据表明，α-肾上腺素D21 A/L-肾上腺素D2-肾上腺素受体主要介导该动脉中对去甲肾上腺素的反应。其他α-D_（21）-D_（22）-肾上腺素受体亚型也可介导该动脉对去甲肾上腺素的次级收缩反应。

项目成果

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Suzuki, Y., Moriyama, et al.: "Age-related change of the role of αィイD21LィエD2-adrenoceptor in canine urethral smooth muscle."General Pharmacologyr. 33. 347-354 (1999)

Suzuki, Y., Moriyama, et al.：“α-D21L-D2-肾上腺素受体在犬尿道平滑肌中的作用与年龄相关的变化。”普通药理学 33. 347-354 (1999)

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Kurooka, Y., et al.：“α_1-肾上腺素受体亚型 mRNA 在人肾皮质中的分布。Br.J.Urol.83 (1999)。

Taki, N, Taniguchi, T, Okada, K, Moriyama, N, et al.: "Evidence for predominant mediation of α_<1L>-adrenoceptor in the tonus of whole urethra of women"J. Urol.. 162. 1829-1832 (1999)

Taki, N, Taniguchi, T, Okada, K, Moriyama, N, et al.：“α_<1L>-肾上腺素受体在女性整个尿道紧张中占主导地位的证据”J. Urol.. 162。 1832 (1999)

Takahashi, M., Taniguchi, T., Murata, S., Okada, K., Moriyama, N., et al.: "New αィイD21ィエD2-adrenoceptor antagonist, JTH-601, shows more than 10 times higher affinity for the human prostates than arteries."Journal of Urology. 161. 1350-1354 (1999)

Takahashi, M.、Taniguchi, T.、Murata, S.、Okada, K.、Moriyama, N.等人：“新型 α D21 D2 肾上腺素受体拮抗剂 JTH-601 对人类前列腺比动脉更重要。”《泌尿外科杂志》。161. 1350-1354 (1999)