Receptor crosstalk protein, calcyon, regulates affinity state of dopamine D1 receptors.
Receptor crosstalk protein, calcyon, regulates affinity state of dopamine D1 receptors.
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受体串扰蛋白 calcyon 调节多巴胺 D1 受体的亲和状态。
DOI：
10.1016/s0014-2999(01)01265-1
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发表时间：
2001
影响因子：
5
通讯作者：
Bergson,C
中科院分区：
文献类型：
--
作者：
Lidow,MS;Roberts,A;Zhang,L;Koh,PO;Lezcano,N;Bergson,C
最近克隆的蛋白calcyon增强了Gs偶联的多巴胺D1受体和异源的GQ/11偶联受体之间的串扰，使多巴胺D1受体除了刺激cAMP的产生外，还刺激细胞内钙离子的释放。这种串扰还需要参与GQ/11偶联的受体被它们的激动剂启动。我们检测了钙调蛋白和启动剂调节多巴胺D_1受体与其配体亲和力的能力。分别对表达多巴胺D1受体的HEK293细胞膜标本进行受体结合实验。多巴胺D1受体和钙蛋白的共同表达既不影响该受体对拮抗剂的亲和力，也不影响激动剂与该受体高亲和力和低亲和力状态的亲和力。然而，钙离子的存在显著降低了高亲和力多巴胺D1受体激动剂结合位点的比例。这种下降被卡巴胆碱逆转，卡巴胆碱通过刺激内源性GQ/11偶联的M受体来启动受体串扰。我们的发现表明，钙调蛋白调节多巴胺D1受体达到激动剂的高亲和力状态的能力，其方式依赖于受体串扰的启动。
The recently cloned protein, calcyon, potentiates crosstalk between Gs-coupled dopamine D1 receptors and heterologous Gq/11-coupled receptors allowing dopamine D1 receptors to stimulate intracellular Ca2+release, in addition to cAMP production. This crosstalk also requires the participating Gq/11-coupled receptors to be primed by their agonists. We examined the ability of calcyon and priming to regulate the affinity of dopamine D1 receptors for its ligands. Receptor binding assays were performed on HEK293 cell membrane preparations expressing dopamine D1 receptors either alone or in combination with calcyon. Co-expression of dopamine D1 receptor and calcyon affected neither the affinity of this receptor for antagonists nor the affinity of agonist binding to this receptor high and low-affinity states. However, the presence of calcyon dramatically decreased the proportion of the high-affinity dopamine D1 receptor agonist binding sites. This decrease was reversed by carbachol, which primes the receptor crosstalk by stimulating endogenous Gq/11-coupled muscarinic receptors. Our findings suggest that calcyon regulates the ability of dopamine D1 receptors to achieve the high-affinity state for agonists, in a manner that depends on priming of receptor crosstalk.