Identification and characterization of novel properties of the human D3 dopamine receptor
Identification and characterization of novel properties of the human D3 dopamine receptor
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DOI：
10.1016/j.mcn.2004.01.014
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发表时间：
2004-05-01
影响因子：
3.5
通讯作者：
Pasuit, J
中科院分区：
文献类型：
--
作者：
Kuzhikandathil, EV;Westrich, L;Pasuit, J
在多巴胺受体中，D3受体亚型的功能和性质知之甚少。在这里，我们报告的两个独特的性质的人D3受体的识别和表征。D3受体表现出耐受性，其中第二激动剂诱导的反应的幅度与第一反应相比降低60%，并且在重复激动剂应用时逐渐降低。此外，与D2多巴胺受体不同，D3受体反应在激动剂去除后终止慢15倍。使用D3/D2 S嵌合受体，我们证明了D3受体耐受性是由一种新的构象机制介导的，涉及D3受体第二胞质区域。慢反应终止速率特性需要第三胞质区域，并且是由于D3受体对配体的高亲和力以及其独特的G蛋白信号传导机制。(C)2004年爱思唯尔公司All rights reserved.
Among dopamine receptors, the function and properties of the D3 receptor subtype are poorly understood. Here we report the identification and characterization of two unique properties of the human D3 receptor. The D3 receptor exhibits a tolerance property wherein the magnitude of the second agonist-induced response is reduced by 60% compared to the first response and progressively decreases upon repeated agonist application. In addition, unlike the D2 dopamine receptor, the D3 receptor response terminates 15-fold more slowly upon agonist removal. Using D3/D2S chimeric receptors, we demonstrate that D3 receptor tolerance property is mediated by a novel conformational mechanism involving the D3 receptor second cytoplasmic region. The slow response termination rate property requires the third cytoplasmic region and is due to the high affinity of the D3 receptor for ligand as well as its unique G-protein signaling mechanism. (C) 2004 Elsevier Inc. All rights reserved.