芋螺镇痛多肽研究进展

Recent advances in study of antinociceptive conotoxins

芋螺多肽由芋螺毒液管和毒囊内壁的毒腺所分泌,大多数芋螺多肽由10～40个氨基酸残基组成,且富含二硫键,能特异性作用于乙酰胆碱受体(nAChR),及钙、钠、钾等多种离子通道亚型。目前已发现作用于N-型钙通道、nAChR的α9α10亚基、TTX-R钠通道、NMDA受体的芋螺多肽具有很强的镇痛活性,其中N-型钙通道抑制剂ω-MVIIA已于2004年上市。该类镇痛多肽具有相对分子质量小、结构稳定、活性及选择性高等特点。芋螺镇痛多肽不仅会成为镇痛机制等相关神经生物学研究的重要工具,也会为开发新一代无致瘾镇痛药起到重要作用。本文对芋螺镇痛多肽研究的最新进展予以评述,着重介绍芋螺镇痛多肽的作用靶位、构效关系及其应用进展。

The Conus venom is secreted by the duct and theca of venom. Most ofconotoxins are composed of 10-40 amino acid residues with several disulfide bridges. They can specifically target neurotransmitter receptors including nAChRs, calcium ion channels, sodium ion channels and potassium ion channels, etc. Some conotoxins, such as that target N-Ca^2＋ channels, nAChR α9α10 subtype, TTX-R Na^＋ channels or NMDA receptors, have potent antinociceptive activities, ω-MVIIA, an Ca^2＋ channels blocker was approved by FDA in December, 2004 for marketing. Because of lower molecular weight and high specificity, conotoxins are the powerful pharmacology tools and potent analgesics without addiction. This review briefly summarizes the research progress of antinociceptive conotoxins and addresses on their targets and structure-activity relationships.