Salgado Vincent L, Saar Raimund
Bayer CropScience AG, Global Biology Insecticides, Alfred-Nobel-Strasse 50, D-40789 Monheim am Rhein, Germany.
J Insect Physiol. 2004 Oct;50(10):867-79. doi: 10.1016/j.jinsphys.2004.07.007.
Two alpha-bungarotoxin-sensitive nicotinic receptor subtypes in cockroach neurons are identified as desensitizing (nAChD), selectively inhibitable with 100 nM imidacloprid, and non-desensitizing (nAChN), selectively inhibitable with 100 pM methyllycaconitine. Although the desensitization rate of nAChD receptors is highly variable, pharmacology is largely independent of desensitization rate. Because desensitized states tightly bind agonists, nAChD receptors are potently inhibited by neonicotinoids and specifically measured in radiolabeled imidacloprid binding assays. However, they are not usually detected in binding assays with radiolabeled alpha-bungarotoxin, which has a Kd for the resting state of 21 nM, but binds poorly to desensitized states often present in binding assays. In contrast, nAChN receptors are specifically measured in binding assays with radiolabeled alpha-bungarotoxin, which binds them with a Kd of 1.3 nM. nAChN receptors are activated by neonicotinoids at micromolar concentrations, and allosterically by spinosyn A, with an EC50 of 27 nM. Spinosyn A weakly antagonizes nAChD receptors -23% at 10 microM. The roles of the two nAChR subtypes in insecticide poisoning are discussed.
蟑螂神经元中的两种α-银环蛇毒素敏感型烟碱受体亚型被鉴定为脱敏型（nAChD），可被100 nM吡虫啉选择性抑制，以及非脱敏型（nAChN），可被100 pM甲基lycaconitine选择性抑制。尽管nAChD受体的脱敏速率变化很大，但其药理学特性在很大程度上与脱敏速率无关。由于脱敏状态会紧密结合激动剂，nAChD受体在新烟碱类药物作用下会受到强烈抑制，并在放射性标记的吡虫啉结合试验中进行特异性检测。然而，它们通常不会在放射性标记的α-银环蛇毒素结合试验中被检测到，α-银环蛇毒素对静息状态的Kd为21 nM，但与结合试验中经常出现的脱敏状态结合不佳。相比之下，nAChN受体在放射性标记的α-银环蛇毒素结合试验中进行特异性检测，α-银环蛇毒素以1.3 nM的Kd与它们结合。nAChN受体在微摩尔浓度下被新烟碱类药物激活，并被多杀菌素A变构激活，EC50为27 nM。多杀菌素A对nAChD受体有弱拮抗作用——在10 μM时为-23%。文中讨论了两种nAChR亚型在杀虫剂中毒中的作用。
