[35S]GTPγS binding at the human dopamine D4 receptor variants hD4.2, hD4.4 and hD4.7 following stimulation by dopamine, epinephrine and norepinephrine
[35S]GTPγS binding at the human dopamine D4 receptor variants hD4.2, hD4.4 and hD4.7 following stimulation by dopamine, epinephrine and norepinephrine
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DOI：
10.1016/j.ejphar.2005.11.063
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发表时间：
2006-02-15
影响因子：
5
通讯作者：
Traynor, J
中科院分区：
文献类型：
--
作者：
Czermak, C;Lehofer, M;Traynor, J
本研究的目的是调查人类多巴胺D4受体48 bp多态性变体hD4.2，hDA之间可能存在的差异。和hD4.7在激动剂刺激的[S-35]GTP γ S结合中，以研究多巴胺D4受体钠敏感性并进一步表征该受体的去甲肾上腺素和肾上腺素激动作用。分别在10和100 mM钠的实验条件下，使用[S-35]GTP γ S测定法研究了多巴胺、去甲肾上腺素和肾上腺素刺激后CHO-K1细胞中表达的受体变体hD4.2、hD4.4和hD4.7的G蛋白活化。与10 mM钠下的hD4.4和hD4.7相比，多巴胺在hD4.2下显示出2倍更高的刺激[S-35]GTP γ S结合的效力。发现基础[S-35]GTP γ S结合的钠敏感性存在显著差异，hD4.7的敏感性是hD4.4的1.7倍，是hD4.2的2.5倍。去甲肾上腺素和肾上腺素在所有三种受体变体上均产生[S-35]GTP γ S结合的浓度依赖性增加，肾上腺素的效力仅比多巴胺低2倍。目前的结果与先前报道的多巴胺D4受体变体之间的功能性2-3倍差异在一定程度上一致。去甲肾上腺素和肾上腺素在多巴胺D4受体上的激动作用可能表明不同单胺神经递质系统之间交叉反应的重要方式。(c)2005 Elsevier B. V.保留所有权利。
Aim of the present study was to investigate possible differences between the human dopamine D4 receptor 48 bp polymorphism variants hD4.2, hDA. and hD4.7 in agonist stimulated [S-35]GTP gamma S binding, to investigate dopamine D4 receptor sodium sensitivity and to further characterize norepinephrine and epinephrine agonism at this receptor. G-protein activation at the receptor variants hD4.2, hD4.4 and hD4.7 expressed in CHO-K1 cells, following stimulation by dopamine, norepinephrine and epinephrine, was investigated using the [S-35]GTP gamma S assay at experimental conditions of 10 and 100 mM sodium, respectively. Dopamine displayed a 2 fold higher potency of stimulating [S-35]GTP gamma S binding at the hD4.2, compared to the hD4.4 and hD4.7 at 10 mM sodium. A significant difference in sodium sensitivity of basal [S-35]GTP gamma S binding was found, with the hD4.7 being 1.7 fold more sensitive than the hD4.4 and 2.5 fold more sensitive than the hD4.2. Norepinephrine and epinephrine both produced concentration-dependent increases in [S-35]GTP gamma S binding at all three receptor variants, and epinephrine showed only 2 fold less potency than dopamine. The present results are in certain line with previous reports of functional 2-3 fold differences between the dopamine D4 receptor variants. Agonism of norepinephrine and epinephrine at the dopamine D4 receptor may indicate an important way of cross-reactivity among the different monoamine neurotransmitter systems. (c) 2005 Elsevier B.V. All rights reserved.