Migrastatin acts as a muscarinic acetylcholine receptor antagonist.
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.
Nakae
Koichi
K
Bioactive Molecules Research Group, Microbial Chemistry Research Center, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. nakaek@bikaken.or.jp
Nishimura
Yoshio
Y
Ohba
Syunichi
S
Akamatsu
Yuzuru
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D005260:Female; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D018942:Macrolides / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019832:N-Methylscopolamine / Q000037:antagonists & inhibitors / Q000378:metabolism; D010881:Piperidones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D007783:Lactones; D018942:Macrolides; D018727:Muscarinic Antagonists; D010881:Piperidones; D011976:Receptors, Muscarinic; C418199:migrastatin; D002217:Carbachol; D000242:Cyclic AMP; D002118:Calcium; D019832:N-Methylscopolamine