Sodium channels resistance mechanisms

In some resistant strains, both types of resistance mechanism have been shown to operate against the same insecticide. Thus, the PEG87 strain of the tobacco bud worm (Heliothis virescens) is resistant to pyrethroids on account of both a highly active form of cytochrome P450 and an insensitive form of the sodium channel (Table 4.3 and McCaffery 1998). 

Resistance to DDT has been developed in many insect species. Although there are some cases of metabolic resistance (e.g., strains high in DDT dehydrochlorinase activity), particular interest has been focused on kdr and super kdr mechanisms based upon aberrant forms of the sodium channel—the principal target for DDT. There are many examples of insects developing resistance to dieldrin. The best-known mechanism is the production of mutant forms of the target site (GABA receptor), which are insensitive to the insecticide. 

Pyrethroids are widely used to control many agriculturally and medically important insect pests. Due to intensive use of pyrethroids in pest control, many pest populations have developed resistance to these compounds. One major mechanism of pyrethroid resistance, conferred by the knock down resistance gene (Mr), is reduced target site (sodium channel) sensitivity to DDT and pyrethroids. Studies on the molecular basis of Mr and Mr-type resistance in various insects are enhancing our understanding of the structure and function of insect sodium channels and the molecular interaction between insect sodium channels and pyrethroids. In this chapter, I will review recent advances in... 

Mechanism of action Pyrethrins and pyrethroids increase the sodium influx into nerve cells by extending the opening periods of certain sodium channels. This leads to an overexcitation especially in invertebrates. Resistance phenomena are based, among others, on a change of the site of action of pyrethrins and pyrethroids. 

Tatebayashi H, Narahashi T (1994) Differential mechanism of action of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther 270 595-603... 

Pediculosis caused by Pediculus capitis, the human head louse, is the most prevalent parasitic infestation of humans worldwide, especially among school children of 3-12 years old (7). More Uian 6-12 million people in the United States (US) are estimated to have pediculosis. Synq>toms of infestations are relatively mild, but the social, mental and economic consequences are substantial. Pediculosis is not widely tolerated in the US and is repeatedly treated by a variety of over-the-counter pediculicides, which are exclusively limited to those containing pyrethrin or permetfarin as active ingredients. Because these pediculicides share a common mechanism of action on the voltage-sensitive sodium channel in the nervous system of insects (2), dieir repetitive and continued use has imposed a high pressure for the selection of resistant louse populations. 

In this article, the level of susceptibility to various insecticides in different human head louse populations in the US was investigated to assess the distribution of resistance. We also reported on the molecular mechanisms of head louse resistance to pyrethroid mediated by sodium channel mutations. Also discussed were the genotyping techniques for resistance monitoring and the... 

---