迁移抑制素作为一种毒蕈碱型乙酰胆碱受体拮抗剂发挥作用。

Migrastatin acts as a muscarinic acetylcholine receptor antagonist.

作者信息

Nakae Koichi, Nishimura Yoshio, Ohba Syunichi, Akamatsu Yuzuru

机构信息

Bioactive Molecules Research Group, Microbial Chemistry Research Center, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.

出版信息

J Antibiot (Tokyo). 2006 Nov;59(11):685-92. doi: 10.1038/ja.2006.91.

DOI:10.1038/ja.2006.91

PMID:17256466

Abstract

Migrastatin and its analogs have various biological activities such as inhibition of cell migration and anchorage-independent growth of cancer cells. Although its biosynthesis and chemical synthesis have been under investigation, little is known about the biological target of migrastatin. Here, we found that migrastatin inhibited intracellular calcium mobilization induced by carbachol in neuroblastoma SK-N-SH cells without affecting Ca2+ mobilization and cAMP accumulation induced by ligands of other receptors. The binding of [3H] N-methylscopolamine, an antagonist for muscarinic receptor was also inhibited by migrastain. Functionally, migrastatin inhibited Ca2+ mobilization induced by carbachol in primary cultures of smooth muscle cells of rat bladder. This study reveals that migrastatin acts as a muscarinic acetylcholine receptor antagonist.

摘要

迁移抑制素及其类似物具有多种生物学活性，如抑制癌细胞的细胞迁移和非贴壁依赖性生长。尽管其生物合成和化学合成一直在研究中，但关于迁移抑制素的生物学靶点知之甚少。在此，我们发现迁移抑制素可抑制神经母细胞瘤SK-N-SH细胞中由卡巴胆碱诱导的细胞内钙动员，而不影响其他受体配体诱导的Ca2+动员和cAMP积累。毒蕈碱受体拮抗剂[3H]N-甲基东莨菪碱的结合也受到迁移抑制素的抑制。在功能上，迁移抑制素可抑制大鼠膀胱平滑肌细胞原代培养物中由卡巴胆碱诱导的Ca2+动员。这项研究表明，迁移抑制素可作为一种毒蕈碱型乙酰胆碱受体拮抗剂。