大鼠肠系膜小动脉α - 1l肾上腺能受体药理学分析。

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Stam WB, Van der Graaf PH, Saxena PR

大鼠肠系膜小动脉α - 1l肾上腺能受体药理学分析。

中国药理学杂志1999年6月;127(3):661-70。

PubMed ID

10401556 (查看PubMed

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摘要

1.为了阐明α - 1A或α - 1l肾上腺素能受体参与去甲肾上腺素素介导的大鼠肠系膜小动脉(SMA)收缩的争议，我们研究了不同实验条件下亚型选择性α - 1肾上腺素能受体激动剂和拮抗剂的作用。2.大鼠SMA中激动剂效价顺序为:A61603 >> SKF89748-A > cirazoline >去甲肾上腺素> ST-587 >甲氧沙明。Prazosin能拮抗所有低效激动剂(pA2: 8.29-8.80)，表明参与α 1l而不是α 1a肾上腺能受体。3.已知的α - 1l肾上腺素能受体拮抗剂JTH-601，而不是α - 1b肾上腺素能受体拮抗剂氯乙可乐定(10 microM)拮抗去甲肾上腺素诱导的SMA收缩。选择性α - 1D-肾上腺素能受体拮抗剂BMY 7378抗去甲肾上腺素(pA2 = 6.16 +/- 0.13)和选择性α - 1a -肾上腺素能受体拮抗剂RS-17053抗去甲肾上腺素(pKB = 8.35 +/- 0.10)和选择性α - 1a -肾上腺素能受体激动剂A-61603 (pKB = 8.40 +/- 0.09)的效力太低，不足以解释α - 1D-和α - 1a -肾上腺素能受体的作用。4.RS-17053 (pKB/pA2's = 7.72-8.46)的药效不受温度降低、实验方法改变和KCl或U46619诱导肌张力的影响。 5. Selective protection of a putative alpha 1A-adrenoceptor population against the irreversible action of phenoxybenzamine also failed to increase the potency of RS-17053 (pA2 = 8.25 +/- 0.06 against A61603). 6. Combined concentration-ratio analysis demonstrated that tamsulosin, which does not discriminate between alpha 1A- and alpha 1L-adrenoceptors, and RS-17053 competed for binding at the same site in the SMA. 7. In summary, data obtained in our experiments in rat SMA indicate that the alpha 1-adrenoceptor mediating noradrenaline-induced contraction displays a distinct alpha 1L-adrenoceptor pharmacology. This study does not provide evidence for the hypothesis that alpha 1L-adrenoceptors represent an affinity state of the alpha 1A-adrenoceptor in functional assays. Furthermore, there is no co-existing alpha 1A-adrenoceptor in the SMA.

引用本文的药库数据

药物靶点

药物	目标	种类	生物	药理作用	行动
酚苄明	阿尔法- 1a肾上腺素能受体	蛋白质	人类	是的	拮抗剂	细节