PMID- 9990721
OWN - NLM
STAT- MEDLINE
DCOM- 19990315
LR  - 20171116
IS  - 0066-4170 (Print)
IS  - 0066-4170 (Linking)
VI  - 44
DP  - 1999
TI  - The insect voltage-gated sodium channel as target of insecticides.
PG  - 429-55
AB  - Examination of the function, chemistry, and pharmacology of the voltage-gated 
      insect sodium channel (ISC) reveals that the ISC closely resembles its vertebrate 
      counterpart in electrophysiology and ion conductance, primary structure and 
      allocation of all functional domains, and its pharmacological diversity and 
      flexibility exhibited by the occurrence of different allosterically coupled 
      receptor-binding sites for various neurotoxicants. The toxicants include several 
      groups of insecticides, namely DDT and its analogues, pyrethroids, N-alkylamides, 
      and dihydropyrazoles, which affect channel gating and ion permeability. Despite 
      their similarity, the insect and vertebrate channels are pharmacologically 
      distinguishable, as revealed by the responsiveness of the heterologously 
      expressed Drosophila para clone to channel modifiers and blockers and the 
      occurrence of the insect-selective sodium channel neurotoxins derived from 
      arachnid venoms presently used for the design of recombinant baculovirus-mediated 
      selective bioinsecticides. The pharmacological specificity of the ISC may lead to 
      the design of insect-selective toxicants, and its pharmacological flexibility may 
      direct the use of ISC insecticides for resistance management. Insecticide 
      resistance [such as knockdown resistance (KDR)] is acquired by natural selection 
      and operated by increased metabolism, channel mutagenesis, or both. The 
      resistance issue can be dealt with in several ways. One is by simultaneous 
      application of low doses of synergistic, allosterically coupled mixtures (thus 
      delaying or preventing the onset of resistance). An alternative is to replace an 
      insecticide to which resistance was acquired by channel mutation with a different 
      ISC toxicant to which increased susceptibility was conferred by the same 
      mutation. Such a possibility was exemplified by a significant increase in 
      susceptibility to N-alkylamides, as well as an insect-selective neurotoxin 
      revealed by KDR insects. Third, both of these methods can be combined. Thus owing 
      to its pharmacological uniqueness, the ISC may serve as a high-priority target 
      for future selective and resistance-manageable insecticides.
FAU - Zlotkin, E
AU  - Zlotkin E
AD  - Department of Cell and Animal Biology, Hebrew University, Jerusalem, Israel. 
      Zlotkin@vms.huji.ac.il
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
PL  - United States
TA  - Annu Rev Entomol
JT  - Annual review of entomology
JID - 0372367
RN  - 0 (Insecticides)
RN  - 0 (Neurotoxins)
RN  - 0 (Sodium Channels)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Drosophila/drug effects/genetics/metabolism
MH  - Gene Expression
MH  - Genes, Insect
MH  - Insecta/*drug effects/genetics/*metabolism
MH  - Insecticide Resistance
MH  - Insecticides/metabolism/*pharmacology
MH  - Neurotoxins/metabolism/pharmacology
MH  - Sodium Channels/*drug effects/genetics/metabolism
MH  - Vertebrates
RF  - 73
EDAT- 1999/02/17 00:00
MHDA- 1999/02/17 00:01
CRDT- 1999/02/17 00:00
PHST- 1999/02/17 00:00 [pubmed]
PHST- 1999/02/17 00:01 [medline]
PHST- 1999/02/17 00:00 [entrez]
AID - 10.1146/annurev.ento.44.1.429 [doi]
PST - ppublish
SO  - Annu Rev Entomol. 1999;44:429-55. doi: 10.1146/annurev.ento.44.1.429.