Cloning and expression of a G protein-linked acetylcholine receptor from Caenorhabditis elegans
Cloning and expression of a G protein-linked acetylcholine receptor from Caenorhabditis elegans
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DOI：
10.1046/j.1471-4159.1999.0720058.x
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发表时间：
1999-01-01
影响因子：
4.7
通讯作者：
Cho, NJ
中科院分区：
文献类型：
--
作者：
Lee, YS;Park, YS;Cho, NJ
我们从秀丽隐杆线虫中分离出一个cDNA克隆，该克隆编码一个与毒蕈碱乙酰胆碱受体序列相似性最大的蛋白质。该基因编码一个由682个氨基酸组成的多肽，包含7个假定的跨膜结构域。除第三胞内环高度可变的中间部分外，氨基酸与人类m1-m5受体的同源性为28-34%。当该克隆受体与G蛋白门控的内向纠偏K+通道（GIRK1）在非洲爪蟾卵母细胞中共表达时，乙酰胆碱能够引发GIRK电流。这种乙酰胆碱诱导的电流被毒蕈碱拮抗剂阿托品以可逆的方式显著抑制。然而，另一种毒蕈碱激动剂氧tremorine和拮抗剂东莨菪碱和哌嗪对该受体的影响很小或可以忽略不计。综上所述，这些结果表明克隆基因编码的G蛋白连接的乙酰胆碱受体与毒蕈碱乙酰胆碱受体最相似，但在药理学上不同。
We have isolated a cDNA clone from the nematode Caenorhabditis elegans that encodes a protein of greatest sequence similarity to muscarinic acetylcholine receptors. This gene codes for a polypeptide of 682 amino acids containing seven putative transmembrane domains. The amino acid identities, excluding a highly variable middle portion of the third intracellular loop, to the human m1-m5 receptors are 28-34%. When this cloned receptor was coexpressed with a G protein-gated inwardly rectifying K+ channel (GIRK1) in Xenopus oocyte, acetylcholine was able to elicit the GIRK current. This acetylcholine-induced current was substantially inhibited by the muscarinic antagonist atropine in a reversible manner. However, another muscarinic agonist oxotremorine and antagonists scopolamine and pirenzepine had little or negligible effects on this receptor. Taken together, these results suggest that the cloned gene encodes a G protein-linked acetylcholine receptor that is most similar to but pharmacologically distinct from muscarinic acetylcholine receptors.