A cDNA encoding the calcitonin gene-related peptide type 1 receptor
A cDNA encoding the calcitonin gene-related peptide type 1 receptor
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DOI：
10.1074/jbc.271.19.11325
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发表时间：
1996-05-10
影响因子：
4.8
通讯作者：
Li, Y
中科院分区：
文献类型：
--
作者：
Aiyar, N;Rand, K;Li, Y
降钙素基因相关肽（CGRP）是一种神经肽，具有多种生物学作用，包括强效的血管扩张活性。我们在此报道了编码人CGRP（1）受体的互补DNA（cDNA）的克隆，该受体与G蛋白偶联受体超家族成员人降钙素受体具有显著的肽序列同源性。北方印迹分析显示，该受体的信使RNA主要在肺和心脏中表达。原位研究表明，在肺的肺泡细胞和心脏的心肌细胞的受体mRNA的具体定位。在人胚肾293（HEK 293）细胞中稳定表达的cDNA产生了特异性的、高亲和力的CGRP结合位点，其药理学和功能特性与天然人CGRP（1）受体非常相似。将这些细胞暴露于CGRP导致cAMP产生增加60倍，其以竞争性方式被CGRP（1）受体拮抗剂CGRP 9-（8-37）抑制。
Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse biological effects including potent vasodilator activity. We report here the cloning of a complementary DNA (cDNA) encoding a human CGRP(1) receptor, which shares significant peptide sequence homology with the human calcitonin receptor, a member of the G-protein coupled receptor superfamily. Northern blot analysis revealed that the messenger RNA for this receptor is predominantly expressed in the lung and heart. In situ studies showed specific localization of the receptor mRNA to alveolar cells in the lung and to cardiac myocytes in the heart. Stable expression of the cDNA in human embryonic kidney 293 (HEK 293) cells produced specific, high affinity binding sites for CGRP that displayed pharmacological and functional properties very similar to native human CGRP(1) receptor. Exposure of these cells to CGRP resulted in a 60-fold increase in cAMP production, which was inhibited in a competitive manner by the CGRP(1) receptor antagonist, CGR9-(8-37).