描述的α1 d-adrenoceptor调停的收缩反应大鼠主动脉去甲肾上腺素。

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肯尼英航,查尔默斯DH,菲尔波特PC,奈勒

描述的α1 d-adrenoceptor调停的收缩反应大鼠主动脉去甲肾上腺素。

Br J杂志。1995年7月,115 (6):981 - 6。

PubMed ID

7582530 (在PubMed

]

文摘

1。大量的α1-adrenoceptor拮抗剂的亲和力是由位移[3 h]哌唑嗪绑定来自克隆人类α1 a-adrenoceptors(先前指定的克隆α1 c亚型),α1 bα1 d和鼠α1 d-adrenoceptors, rat-1成纤维细胞中稳定表达。功能关联预估这些化合物也决定从大鼠主动脉noradrenaline-mediated收缩。2。我7378显示高亲和力的克隆人类α1 d-adrenoceptors (pKi = 8.2 + / - 0.10),选择性α1 (pKi = 6.2 + / - 0.10)和α1 b亚型(6.7 + / - 0.11)。4101年世行,benoxathian和酚妥拉明显示高度的亲和力α1和α1 d相比肾上腺素能受体α1 b亚型。Spiperone显示高亲和力和选择性α1肾上腺素能受体b (pKi 8.8 + / - 0.16)。5-Methyl-urapidil是克隆选择性α1肾上腺素能受体。3所示。比较结合亲和力(pKi)化合物在克隆人类和rat1D肾上腺素能受体是几乎相同的斜率(r = 0.99, = 1.08)。 4. Prazosin, doxazosin and 5-methyl-urapidil were potent, competitive antagonists of noradrenaline-mediated contractions of rat aorta (pA2 values of 9.8, 8.8 and 7.8 respectively). The selective alpha 1D antagonist BMY 7378 was also a potent antagonist on rat aorta (pKB = 8.3 +/- 0.1) but the interaction of this compound was not consistent with competitive antagonism at a single population of receptors. 5. Functional affinities for compounds determined against noradrenaline-mediated contractions of rat aorta correlated well with binding affinities at cloned alpha 1D-adrenoceptors (r = 0.96), but not with alpha 1A (r = 0.61) or alpha 1B (r = 0.46) subtypes. 6. Noradrenaline-mediated contractions of rat aorta were sensitive to the alkylating effects of chlorethylclonidine (CEC). CEC (10 microM) caused a small rightward shift in the noradrenaline concentration-response curve. CEC at 100 microM caused a further shift and suppression of the maximum response to noradrenaline.7. The results of this study suggest that noradrenaline predominantly, but not exclusively, mediates contraction of rat aorta through the activation of an alphalD-adrenoceptor.

DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
Droxidopa	Alpha-1D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	Alpha-1D肾上腺素能受体	蛋白质	人类	是的	受体激动剂	细节