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Enhanced Neurotransmitter Release by Pyrethroid Insecticides

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Insecticide Action

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Abstract

Using a perfusion system, synaptosomes prepared from rat brain released 3H-norepinephrine in a Ca2+-dependent manner when pulse depolarized by briefly elevating external potassium concentrations. Tetrodotoxin (10−7M) inhibited 48% of the pulsed release and D595 (10−5M), a phenethylamine-type calcium channel blocker, inhibited 27%. In combination, these two specific ion channel antagonists appear to function independently of each other in an additive fashion. Pretreatment of this preparation with deltamethrin resulted in an enhanced release of norepinephrine which occurred in a biphasic fashion with a greater enhancement evident in the second or tailing peak when compared to release in both the presence and absence of tetrodotoxin. Addition of deltamethrin to D595-pretreated synaptosomes resulted in no significant enhancement of release from either peak. This indicates that deltamethrin may be enhancing norepinephrine release by increasing the uptake of Ca2+ via other voltage-gated channels (e.g., calcium) or ion-selective transporters in addition to its action at voltage-gated sodium channels. To determine whether deltamethrin may also have an effect on intraterminal Ca2+ homeostasis, external Ca2+ was replaced with Ba2+ and synaptosomes depolarized with pentylenetetrazol. Deltamethrin enhanced neurotransmitter release over that induced by pentylenetetrazol alone with an estimated ED50 value calculated to be 2.4 × 10−10 M. It is concluded that Type II pyrethroids may be acting as voltage-gated channel agonists in a manner consistent with their structure and activity relationship to the phenethylamine-type calcium channel blockers.

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  1. Department of Entomology, University of Massachusetts, Amherst, MA, USA

    J. Marshall Clark & Jacques R. Marion

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  1. Northwestern University Medical School, Chicago, Illinois, USA

    Toshio Narahashi

  2. Mississippi State University, Mississippi State, Mississippi, USA

    Janice E. Chambers

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Clark, J.M., Marion, J.R. (1989). Enhanced Neurotransmitter Release by Pyrethroid Insecticides. In: Narahashi, T., Chambers, J.E. (eds) Insecticide Action. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1324-3_8

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