Beta-blockers show inverse agonism to a novel constitutively active mutant of β1-adrenoceptor
Beta-blockers show inverse agonism to a novel constitutively active mutant of β1-adrenoceptor
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DOI：
10.1254/jphs.fp0060640
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发表时间：
2006-10-01
影响因子：
3.5
通讯作者：
Nagatomo, Takafumi
中科院分区：
文献类型：
--
作者：
Ahmed, Maruf;Muntasir, Habib Abul;Nagatomo, Takafumi
我们通过点突变获得了一种新的β 1-肾上腺素能受体（β 1-AR）突变体，该突变体能够组成性激活β 1-AR。第二次跨膜中β（1）-AR的天冬氨酸104被丙氨酸取代。在人胚肾（HEK）-293细胞中表达的β（1）-AR突变体与野生型相比具有较高的组成性活性（P < 0.05），并可被某些β受体阻滞剂部分抑制。突变体的组成型活性通过发现增强的活性依赖于受体表达水平而得到证实。本研究的结果可能对未来旨在阐明β（1）-AR激活过程以及β-受体阻滞剂作用机制的研究具有有趣的意义。
We obtained a new mutant of the beta(1)-adrenergic receptor (beta(1)-AR) by point mutations that can constitutively activate beta(1)-AR. Aspartate104 of the beta(1)-AR in the 2nd transmembrane was replaced with alanine. The beta(1)-AR mutant expressed in human embryonic kidney (HEK)-293 cells displayed high level of constitutive activity with respect to wild-type (P < 0.05), which could be partially inhibited by some beta-blockers. The constitutive activity of the mutant was confirmed by the finding that the enhanced activity is dependent on the level of receptor expression. The results of this study might have interesting implications for future studies aiming at elucidating the activation process of the beta(1)-AR as well as the mechanism of action of beta-blockers.