Mutations of the para sodium channel of Drosophila melanogaster identify putative binding sites for pyrethroids.
Mutations of the para sodium channel of Drosophila melanogaster identify putative binding sites for pyrethroids.
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果蝇对钠通道的突变确定了拟除虫菊酯的假定结合位点。
DOI：
10.1124/mol.64.4.914
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发表时间：
2003
影响因子：
3.6
通讯作者：
P.N.R. Usherwood
中科院分区：
文献类型：
--
作者：
H. Vais;Shannon Atkinson;F. Pluteanu;S. Goodson;A. Devonshire;Martin S. Williamson;P.N.R. Usherwood
研究了两种拟除虫菊酯对黑胃果蝇重组野生型和突变型（耐拟除虫菊酯）Na+通道的影响。三个突变（kdr/superkdr）被单独或联合插入到D. melanogaster的para Na+通道中：IIS6结构域的L1014F， IIS4-S5连接体的M918T和IIS5结构域的T929I。采用电压钳法研究了非洲爪蟾卵母细胞中通道的表达，并研究了拟除虫菊酯（ⅰ型）和溴氰菊酯（ⅱ型）对Na+电流的影响。在溴氰菊酯处理后，Na+通道缓慢失活，由此产生的“尾部”电流被用来量化这种拟除虫菊酯类杀虫剂的影响。溴氰菊酯在野生型通道和突变体L1014F通道上作用的Hill斜率为2，表明这些通道上的两个或多个位点存在协同结合。相反，与突变体M918T和T929I的结合是非合作的。野生型通道和L1014F通道的尾电流呈双相衰减，而M918T和T929I突变体的尾电流呈单相衰减。L1014F突变体对溴氰菊酯的敏感性比野生型低约20倍。令人惊讶的是，双突变体M918T+L1014F对溴氰菊酯的敏感性与单独的M918T相似，而T929I+L1014F对溴氰菊酯的敏感性比T929I低10万倍。氯菊酯的效价低于溴氰菊酯，其与各通道类型的结合均不合作。氯菊酯诱导尾电流的衰减完全是单相的。这些发现讨论了拟除虫菊酯结合位点的性质和可能的位置在D. melanogaster Na+通道。
The effects of two pyrethroids on recombinant wild-type and mutant (pyrethroid-resistant) Na+ channels of Drosophila melanogaster have been studied. Three mutations that confer resistance (kdr/superkdr) to pyrethroids were inserted, either individually or in combination, into the para Na+ channel of D. melanogaster: L1014F in domain IIS6, M918T in the IIS4-S5 linker, and T929I in domain IIS5. Channels were expressed in Xenopus laevis oocytes and the effects of the pyrethroids permethrin (type I) and deltamethrin (type II) on Na+ currents were investigated using voltage clamp. The Na+ channels deactivated slowly after deltamethrin treatment, the resultant "tail" currents being used to quantify the effects of this pyrethroid. The Hill slope of 2 for deltamethrin action on the wild-type channel and the mutant L1014F channel is indicative of cooperative binding at two or more sites on these channels. In contrast, binding to the mutants M918T and T929I is noncooperative. Tail currents for the wild-type channel and L1014F channel decayed biphasically, whereas those for M918T and T929I mutants decayed monophasically. The L1014F mutant was approximately 20-fold less sensitive than the wild-type to deltamethrin. Surprisingly, the sensitivity of the double mutant M918T+L1014F to deltamethrin was similar to that of M918T alone, whereas the sensitivity of T929I+L1014F was >30,000-fold lower than that of T929I. Permethrin was less potent than deltamethrin, and its binding to all channel types was noncooperative. The decays of permethrin-induced tail currents were exclusively monophasic. These findings are discussed in terms of the properties and possible locations of pyrethroid binding sites on the D. melanogaster Na+ channel.
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胺菊酯和溴氰菊酯调节河豚毒素敏感和河豚毒素抗性钠通道的动力学。
DOI：
--
发表时间：
2001
期刊：
The Journal of pharmacology and experimental therapeutics.
影响因子：
--
作者：
Tabarean,IV;Narahashi,T
通讯作者：
Narahashi,T
影响因子：
3.8
作者：
Lee, SH;Smith, TJ;Soderlund, DM
通讯作者：
Soderlund, DM
DOI：
--
发表时间：
1994-08
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
H. Tatebayashi;T. Narahashi
通讯作者：
H. Tatebayashi;T. Narahashi
影响因子：
3.8
作者：
Tan, J;Liu, Z;Dong, K
通讯作者：
Dong, K
Nav1.4 电压门控 Na( ) 通道中 D3-S6 段的苯丙氨酸残基对于拟除虫菊酯的作用至关重要。
DOI：
--
发表时间：
2001
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Wang,SY;Barile,M;Wang,GK
通讯作者：
Wang,GK