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Advances in the Mode of Action of Pyrethroids

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Pyrethroids

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 314))

Abstract

The ability to clone, express, and electrophysiologically measure currents carried by voltage-gated ion channels has allowed a detailed assessment of the action of pyrethroids on various target proteins.

Recently, the heterologous expression of various rat brain voltage-gated sodium channel isoforms in Xenopus laevis oocytes has determined a wide range of sensitivities to the pyrethroids, with some channels virtually insensitive and others highly sensitive. Furthermore, some isoforms show selective sensitivity to certain pyrethroids and this selectivity can be altered in a state-dependent manner. Additionally, some rat brain isoforms are apparently more sensitive to pyrethroids than the corresponding human isoform. These finding may have significant relevance in judging the merit and value of assessing the risk of pyrethroid exposures to humans using toxicological studies done in rat.

Other target sites for certain pyrethroids include the voltage-gated calcium and chloride channels. Of particular interest is the increased effect of Type II pyrethroids on certain phosphoforms of the N-type Cav2.2 calcium channel following post-translational modification and its relationship to enhanced neurotransmitter release seen in vivo.

Lastly, parallel neurobehavioral and mechanistic studies on three target sites suggest that a fundamental difference exists between the action of Types I and II pyrethroids, both on a functional and molecular level. These differences should be considered in any future risk evaluation of the pyrethroids.

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Acknowledgment

Partial support for Steven B. Symington is provided by the RI-INBRE Award # P20RR016457-10 from the National Center for Research Resources (NCRR), NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCRR or the NIH.

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  1. University of Massachusetts, Amherst, MA, USA

    J. Marshall Clark

  2. Salve Regina University, Newport, RI, USA

    Steven B. Symington

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  1. Dainihon Jochugiku Co. Ltd., 1-chome, Daikoku-cho, Toyonaka-shi 1-11, Osaka, 561-0827, Japan

    Noritada Matsuo

  2. Sumitomo Chemical Co.Ltd., Takatsukasa 4-2-1, Takarazuka-city, 665-8555, Hyogo, Japan

    Tatsuya Mori

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Clark, J.M., Symington, S.B. (2011). Advances in the Mode of Action of Pyrethroids. In: Matsuo, N., Mori, T. (eds) Pyrethroids. Topics in Current Chemistry, vol 314. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2011_268

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