Nachman R J, Olender E H, Roberts V A, Holman G M, Yamamoto D
Veterinary Entomology Research Unit, FAPRL, U.S. Department of Agriculture, Agricultural Research Service, College Station, TX 77845, USA.
Peptides. 1996;17(2):313-20. doi: 10.1016/0196-9781(95)02097-7.
Benzethonium chloride (Bztc) is the first totally nonpeptide ligand for an insect, indeed an invertebrate, peptide receptor. Bztc mimics the inhibitory physiological activity of the myosuppressins, a subfamily of the FLRFamides, in three different insect bioassay systems. The inhibitory action of leucomyosuppressin and the nonpeptide Bztc in both the cockroach hindgut and the mealworm neuromuscular junction can be blocked by the lipoxygenase inhibitor, nordihydroguaiaretic acid, providing evidence for similar modes of action. Lipoxygenase metabolites of arachidonic acid may mediate inhibition of neuromuscular transmission by these two factors. In addition, Bztc competitively displaces a radiolabeled myosuppressin analogue from high- and low-affinity receptors of the locust oviduct. Thus, the nonpeptide interacts with both binding and activating regions of myosuppressin receptors. Molecular dynamics experiments in which selected functional groups of Bztc were fit onto corresponding functional groups of low-energy myosuppressin pentapeptide structures indicate how Bztc may mimic the myosuppressins at a molecular level. The discovery of Bztc as a nonpeptidal peptidomimetic analogue provides an opportunity to develop new pest management strategies by targeting an insect's own peptide receptor.
苄索氯铵（Bztc）是首个针对昆虫（实际上是无脊椎动物）肽受体的完全非肽类配体。在三种不同的昆虫生物测定系统中，Bztc模拟了肌抑制素（FLRFamides的一个亚家族）的抑制性生理活性。脂氧合酶抑制剂去甲二氢愈创木酸可阻断亮肌抑制素和非肽Bztc在蟑螂后肠和黄粉虫神经肌肉接头处的抑制作用，这为它们类似的作用方式提供了证据。花生四烯酸的脂氧合酶代谢产物可能介导这两种因子对神经肌肉传递的抑制。此外，Bztc能从蝗虫输卵管的高亲和力和低亲和力受体上竞争性地取代放射性标记的肌抑制素类似物。因此，这种非肽与肌抑制素受体的结合区和激活区都相互作用。分子动力学实验将Bztc的选定官能团与低能量肌抑制素五肽结构的相应官能团进行匹配，揭示了Bztc在分子水平上可能如何模拟肌抑制素。Bztc作为一种非肽类拟肽类似物的发现，为通过靶向昆虫自身的肽受体来开发新的害虫管理策略提供了契机。
