Effects of the oxadiazine insecticide indoxacarb, DPX-MP062, on neuronal nicotinic acetylcholine receptors in mammalian neurons

X. Zhao, K. Nagata, W. Marszalec, J. Z. Yeh, T. Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The effects of the novel oxadiazine insecticide DPX-MP062 and its metabolite (DCJW) on neuronal nicotinic acetylcholine receptors (AChRs) were investigated using the whole-cell patch clamp technique in rat embryonic cerebral cortical neurons in primary culture. DPX-MP062, applied at concentrations of 1 and 10 μM to the bath, reduced the peak amplitude of ACh-induced, rapidly decaying currents to 46.8 ± 8.8% (n = 9) and 15.7 ± 5.0% (n = 4) of the control, respectively. The effect was irreversible after washing with drug-free solution. DCJW at either 1 μM or 10 μM had similar actions but the potency was much less than that of DPX-MP062. The slowly desensitizing currents induced by low concentrations of ACh (0.1-10 μM) were augmented and those induced by high concentrations of ACh (100-1000 μM) were inhibited by 10 μM DPX-MP062 with great acceleration of the current decay in a time-dependent manner. These effects were use independent and reversible after washing with drug-free solution. In contrast, DCJW at 10 μM did not show significant effects on peak amplitude and decay phase of the slowly desensitizing ACh-induced current in cortical neurons. These results indicate that the oxadiazine insecticide DPX-MP062 has potent modulating actions on neuronal nicotinic AChRs. The neuronal nicotinic AChR could be one of the primary target sites of the insecticide in mammals.

Original languageEnglish (US)
Pages (from-to)561-570
Number of pages10
JournalNeuroToxicology
Volume20
Issue number4
StatePublished - 1999

Keywords

  • Cortical Neuron
  • DPX- MP062
  • Indoxacarb
  • Insecticide
  • Nicotinic Acetylcholine Receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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