Cloning and characterization of a novel endothelin receptor subtype in the avian class

Cloning and characterization of a novel endothelin receptor subtype in the avian class
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DOI:
10.1073/pnas.95.6.3024
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发表时间:
1998-03-17
影响因子:
11.1
通讯作者:
Le Douarin, NM
Le Douarin, NM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lecoin, L;Sakurai, T;Le Douarin, NM

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内皮素3(Endothelin 3,EDN 3)和内皮素受体B(endothelin receptor B,EDNRB)参与神经嵴的发育,特别是黑素细胞和肠神经系统的发育。我们以前报道过,在嵴细胞迁移之前的神经褶中,EDNRB基因表达,后来在所有的神经嵴衍生物中表达,除了在任何发育阶段的黑素细胞谱系中。鹌鹑成黑素细胞在体外对EDN 3刺激有反应地增殖。这些观察结果促使我们寻找另一种类型的内皮素受体(EDNR)。我们在这里报告通过逆转录酶-PCR克隆了一个编码EDNR亚型的鸟类cDNA,我们称之为EDNRB 2,因为其推导的氨基酸序列与EDNRB的氨基酸序列比哺乳动物EDNRA或爪蟾EDNRC更密切相关。其表达模式不同于“经典”禽类EDNRB,因为其在成黑素细胞和黑素细胞中强烈表达。EDNRB 2转录物在肝脏和肾脏中也是丰富的。我们的药理学研究表明,EDNRB 2与EDN 1、EDN 2和EDN 3以相似的亲和力结合,进一步证实该受体属于B型,尽管它对已知的EDNRB选择性激动剂萨拉福毒素-c显示出低亲和力。
Endothelin 3 (EDN 3) and the endothelin receptor B (EDNRB) are involved in the development of neural crest and particularly of the melanocytes and the enteric nervous system, We reported previously that the avian EDNRB gene is expressed in the neural fold before crest cell migration and later on in all the neural crest derivatives except, at any developmental stage, in the melanocytic lineage, However, quail melanoblasts proliferate in response to EDN 3 stimulation in vitro. These observations prompted us to search for another type of endothelin receptor (EDNR), We report here the cloning by reverse transcriptase-PCR of an avian cDNA encoding a subtype of EDNR, which we have called EDNRB2, because its deduced amino acid sequence is more closely related to that of EDNRB than to either the mammalian EDNRA or to the Xenopus EDNRC. Its expression pattern differs from that of the "classical" avian EDNRB because it is strongly expressed in melanoblasts and melanocytes. EDNRB2 transcripts are also abundant in the liver and kidney, Our pharmacological studies showed that EDNRB2 binds with similar affinity to EDN 1, EDN 2, and EDN 3, further confirming that this receptor belongs to the B type, although it displays a low affinity for sarafotoxin-c, a known EDNRB-selective agonist.