神经元钙通道拮抗剂。利用来自芋螺毒液的ω-芋螺毒素区分钙通道亚型。

Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom.

作者信息

Olivera B M, Cruz L J, de Santos V, LeCheminant G W, Griffin D, Zeikus R, McIntosh J M, Galyean R, Varga J, Gray W R

出版信息

Biochemistry. 1987 Apr 21;26(8):2086-90. doi: 10.1021/bi00382a004.

Abstract

The omega-conotoxins from the venom of fish-hunting cone snails are probably the most useful of presently available ligands for neuronal Ca channels from vertebrates. Two of these peptide toxins, omega-conotoxins MVIIA and MVIIB from the venom of Conus magus, were purified. The amino acid sequences show significant differences from omega-conotoxins from Conus geographus. Total synthesis of omega-conotoxin MVIIA was achieved, and biologically active radiolabeled toxin was produced by iodination. Although omega-conotoxins from C. geographus (GVIA) and C. magus (MVIIA) appear to compete for the same sites in mammalian brain, in amphibian brain the high-affinity binding of omega-conotoxin MVIIA has narrower specificity. In this system, it is demonstrated that a combination of two omega-conotoxins can be used for biochemically defining receptor subtypes and suggested that these correspond to subtypes of neuronal Ca2+ channels.

摘要

来自食鱼圆锥蜗牛毒液中的ω-芋螺毒素可能是目前可获得的用于脊椎动物神经元钙通道的最有用配体。从魔法芋螺毒液中纯化出了两种此类肽毒素，即ω-芋螺毒素MVIIA和MVIIB。其氨基酸序列与地纹芋螺的ω-芋螺毒素有显著差异。实现了ω-芋螺毒素MVIIA的全合成，并通过碘化产生了具有生物活性的放射性标记毒素。尽管来自地纹芋螺（GVIA）和魔法芋螺（MVIIA）的ω-芋螺毒素似乎在哺乳动物脑中竞争相同的位点，但在两栖动物脑中，ω-芋螺毒素MVIIA的高亲和力结合具有更窄的特异性。在该系统中，证明了两种ω-芋螺毒素的组合可用于生物化学定义受体亚型，并表明这些亚型对应于神经元Ca2+通道的亚型。