Advances in the Mode of Action of Pyrethroids
- J. Marshall ClarkAffiliated withUniversity of Massachusetts Email author
- , Steven B. SymingtonAffiliated withSalve Regina University
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.
KeywordsCS-syndrome Neurotransmitter release Pyrethroids T-syndrome Voltage-gated calcium channels Voltage-gated sodium channels
- Advances in the Mode of Action of Pyrethroids
- Book Title
- Book Subtitle
- From Chrysanthemum to Modern Industrial Insecticide
- pp 49-72
- Print ISBN
- Online ISBN
- Series Title
- Topics in Current Chemistry
- Series Volume
- Series ISSN
- Springer Berlin Heidelberg
- Copyright Holder
- Springer-Verlag Berlin Heidelberg
- Additional Links
- Neurotransmitter release
- Voltage-gated calcium channels
- Voltage-gated sodium channels
- Industry Sectors
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- Editor Affiliations
- ID1. Dainihon Jochugiku Co. Ltd.
- ID2. Sumitomo Chemical Co.Ltd.
- Author Affiliations
- 1. University of Massachusetts, Amherst, MA, USA
- 2. Salve Regina University, Newport, RI, USA
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