Chicchi G G, Gimenez-Gallego G, Ber E, Garcia M L, Winquist R, Cascieri M A
Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065-0900.
J Biol Chem. 1988 Jul 25;263(21):10192-7.
An inhibitor of apamin binding has been purified to homogeneity in three chromatographic steps from the venom of the scorpion, Leiurus quinquestriatus hebraeus. The inhibitor, which we have named leiurotoxin I, represents less than 0.02% of the venom protein. It is a 3.4-kDa peptide with little structural homology to apamin although it has some homology to other scorpion toxins such as charybdotoxin, noxiustoxin, and neurotoxin P2. Leiurotoxin I completely inhibits 125I-apamin binding to rat brain synaptosomal membranes (Ki = 75 pM). Thus, it is 10-20-fold less potent than apamin. Leiurotoxin I is not a strictly competitive inhibitor of this binding reaction. Like apamin, leiurotoxin I blocks the epinephrine-induced relaxation of guinea pig teniae coli (ED50 = 6.5 nM), while having no effect on the rate or force of contraction in guinea pig atria or rabbit portal vein preparations. Thus, leiurotoxin I of scorpion venom and apamin of honeybee venom demonstrate similar activities in a variety of tissues, yet are structurally unrelated peptides. These two peptides should be useful in elucidating the role of the small conductance, Ca2+-activated K+ channels in different tissues.
一种抑制蜂毒明肽结合的物质已通过三步色谱法从以色列金蝎毒液中纯化至同质。我们将这种抑制剂命名为 Leiurotoxin I，它在毒液蛋白中所占比例不到 0.02%。它是一种 3.4 kDa 的肽，与蜂毒明肽的结构同源性很低，不过与其他蝎毒素如大蝎毒素、noxius 毒素和神经毒素 P2 有一些同源性。Leiurotoxin I 完全抑制 125I-蜂毒明肽与大鼠脑突触体膜的结合（Ki = 75 pM）。因此，其效力比蜂毒明肽低 10 - 20 倍。Leiurotoxin I 不是这种结合反应的严格竞争性抑制剂。与蜂毒明肽一样，Leiurotoxin I 可阻断肾上腺素诱导的豚鼠结肠带松弛（ED50 = 6.5 nM），而对豚鼠心房或兔门静脉制备物的收缩速率或力量没有影响。因此，蝎毒的 Leiurotoxin I 和蜂毒的蜂毒明肽在多种组织中表现出相似的活性，但它们是结构不相关的肽。这两种肽在阐明小电导、Ca2+ 激活的 K+ 通道在不同组织中的作用方面应该会很有用。
