α - 1a肾上腺素受体介导大鼠离体尾动脉去甲肾上腺素收缩反应的药理特性。

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Lachnit WG, Tran AM, Clarke DE, Ford AP

α - 1a肾上腺素受体介导大鼠离体尾动脉去甲肾上腺素收缩反应的药理特性。

中华药物学杂志，1997 3;120(5):819-26。

PubMed ID

9138687 (PubMed视图

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摘要

1.用受体定量药理学方法研究了α - 1肾上腺素受体群体介导大鼠尾动脉收缩的特征。2.去甲肾上腺素(NA)的累积浓度效应(E/[A])曲线得出p[A]50 = 5.56 +/- 0.05 (n = 16)。Prazosin引起E/[A]曲线向NA的浓度依赖性平行右旋移位，pKb为8.9(席尔德回归斜率= 1.0)。RS-17053 (N-[2-(2-环丙基甲氧基苯氧基)乙基]-5-氯- α， α -二甲基- 1h -吲哚- 3-乙胺盐酸盐;10-100 nM)是一种选择性α 1 a肾上腺素受体拮抗剂，可使E/[a]曲线向NA方向发生非平行、双相、右旋移位，表明涉及不止一种α 1肾上腺素受体亚型。对高亲和成分进行分析，得到表观pA2值为9.2 +/- 0.3。3.a -61603是α 1A肾上腺素受体的选择性激动剂，相对于NA表现为完全激动剂，并产生单相E/[a]曲线，p[A50]为7.59 +/- 0.04 (n = 15)。 Pretreatment of tissues with chloroethylclonidine (CEC; 100 microM for 20 min, followed by 40 min washout), which preferentially alkylates alpha 1B- and alpha 1D-adrenoceptors, did not alter E/[A] curves to A-61603. Prazosin (3-300 nM) caused concentration-dependent, parallel, dextral shifts of E/[A] curves to A-61603 yielding a pA2 estimate of 9.2 +/- 0.2. 4. Experiments with alpha 1-adrenoceptor antagonists of varying subtype selectivities (RS-17053, SNAP 5089, tamsulosin, 5-methylurapidil, BMY 7378, HV 723 and REC 15/2739) revealed parallel dextral shifts of E/[A] curves to A-61603. Schild regression analyses yielded pA2 estimates of 9.2, 9.3, 11.2, 9.0, 6.3, 8.7 and 10.0 for RS-17053, SNAP 5089, tamsulosin, 5-methylurapidil, BMY 7378, HV 723 and REC 15/2739, respectively, although deviations from unit slope (possibly reflecting a secondary involvement of another alpha 1-adrenoceptor) hindered estimations of pKb for some antagonists. The antagonist affinity profile obtained reflects best that described for the alpha 1A-adrenoceptor. 5. In conclusion, caudal artery of rat contracts in response to NA via activation of at least two alpha 1-adrenoceptor subtypes. One of these subtypes displays the pharmacology of the alpha 1A-adrenoceptor, while the other remains to be defined. Use of the novel selective agonist, A-61603, allows for limited pharmacological isolation of the alpha 1A-adrenoceptor permitting characterization of the properties of selective antagonists.

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药物靶点

药物	目标	种类	生物	药理作用	行动
Droxidopa	α - 1a肾上腺素能受体	蛋白质	人类	是的	受体激动剂	细节
去甲肾上腺素	α - 1a肾上腺素能受体	蛋白质	人类	是的	受体激动剂	细节