Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1)
Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1)
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DOI：
10.1016/s0014-5793(99)01092-3
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发表时间：
1999-09-03
期刊：
影响因子：
3.5
通讯作者：
Richter, D
中科院分区：
文献类型：
--
作者：
B채chner, D;Kreienkamp, HJ;Richter, D
为了确定孤儿生长抑素样受体1(SLC-1)的可能配体，利用注射了编码SLC-1的CRNAs和G蛋白门控内向整流钾通道(GIRK)的大鼠卵母细胞功能表达系统，观察到大鼠脑粗提物有很强的内向电流，经阳离子交换层析和高效液相色谱(HPLC)进一步纯化后，获得了两个具有高激动剂活性的多肽。质谱学和部分肽序列分析表明，其中一个与神经肽黑素浓缩激素完全相同，另一个代表截短的黑色素浓缩激素，缺少S末端的三个氨基酸残基。表达MCH受体的非洲爪哇卵母细胞对合成MCH的NM浓度的反应不仅通过激活GIRK介导的电流，还通过诱导磷脂酶C介导的钙依赖氯电流来实现。这表明MCH受体可以偶联到G(I)或G(Q)介导的信号转导途径，这表明MCH可能参与包括食物摄取行为在内的许多不同的大脑功能。(C)1999年欧洲生化学会联合会。
To identify possible ligands of the orphan somatostatin-like receptor 1 (SLC-1), rat brain extracts mere analyzed by using the functional expression system of Xenopus oocytes injected with cRNAs encoding SLC-1 and G protein-gated inwardly rectifying potassium channels (GIRK), A strong inward current was observed with crude rat brain extracts which upon further purification by cation exchange chromatography and high performance liquid chromatography (HPLC) yielded two peptides with a high agonist activity. Mass spectrometry and partial peptide sequencing revealed that one peptide is identical,vith the neuropeptide melanin concentrating hormone (MCH), the other represents a truncated version of MCH lacking the three S-terminal amino acid residues. Xenopus oocytes expressing the MCH receptor responded to nM concentrations of synthetic MCH not only by the activation of GIRK-mediated currents but also by the induction of Ca2+ dependent chloride currents mediated by phospholipase C. This indicates that the MCH receptor can couple either to the G(i)- or G(q)-mediated signal transduction pathway, suggesting that MCH may serve for a number of distinct brain functions including food uptake behavior. (C) 1999 Federation of European Biochemical Societies.