气候变化领域集成服务门户(CCPortal): Mambalgin-3 potentiates human acid-sensing ion channel 1b under mild to moderate acidosis: Implications as an analgesic lead

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DOI	10.1073/pnas.2021581118
	Mambalgin-3 potentiates human acid-sensing ion channel 1b under mild to moderate acidosis: Implications as an analgesic lead
	Cristofori-Armstrong B.; Budusan E.; Rash L.D.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	Acid-sensing ion channels (ASICs) are expressed in the nervous system, activated by acidosis, and implicated in pain pathways. Mambalgins are peptide inhibitors of ASIC1 and analgesic in rodents via inhibition of centrally expressed ASIC1a and peripheral ASIC1b. This activity has generated interest in mambalgins as potential therapeutics. However, most mechanism and structure–activity relationship work on mambalgins has focused on ASIC1a, and neglected the peripheral analgesic target ASIC1b. Here, we compare mambalgin potency and mechanism of action at heterologously expressed rat and human ASIC1 variants. Unlike the nanomolar inhibition at ASIC1a and rodent ASIC1b, we find mambalgin-3 only weakly inhibits human ASIC1b and ASIC1b/3 under severe acidosis, but potentiates currents under mild/moderate acidosis. Our data highlight the importance of understanding the activity of potential ASIC-targeting pharmaceuticals at human channels. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Acid-sensing ion channel; Analgesic; Mambalgin
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180514
作者单位	School of Biomedical Sciences, Faculty of Medicine, University of Queensland, St Lucia, QLD 4072, Australia
推荐引用方式 GB/T 7714	Cristofori-Armstrong B.,Budusan E.,Rash L.D.. Mambalgin-3 potentiates human acid-sensing ion channel 1b under mild to moderate acidosis: Implications as an analgesic lead[J],2021,118(8).
APA	Cristofori-Armstrong B.,Budusan E.,&Rash L.D..(2021).Mambalgin-3 potentiates human acid-sensing ion channel 1b under mild to moderate acidosis: Implications as an analgesic lead.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Cristofori-Armstrong B.,et al."Mambalgin-3 potentiates human acid-sensing ion channel 1b under mild to moderate acidosis: Implications as an analgesic lead".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).