Insect Control: Biological and Synthetic Agents - Index of
Insect Control: Biological and Synthetic Agents - Index of
Insect Control: Biological and Synthetic Agents - Index of
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Figure 13 Diagrammatic representation <strong>of</strong> the location <strong>of</strong> the<br />
binding sites associated with the S6 segments <strong>of</strong> the Na þ channel.<br />
The extracellular mouth <strong>of</strong> the channel is at the top <strong>of</strong> the<br />
figure. Two sets <strong>of</strong> the S4, S5, <strong>and</strong> S6 transmembrane helices<br />
are shown. Bidirectional arrows show the movements <strong>of</strong> the S4<br />
<strong>and</strong> S6 segments associated with activation gating. The thick<br />
solid curves show the outline <strong>of</strong> the channel protein in the<br />
activated or open conformation, <strong>and</strong> the thick dotted line<br />
shows the activation gate at the cytoplasmic end <strong>of</strong> the S6 segments<br />
in the closed position. There is one tetrodotoxin (TTX) <strong>and</strong><br />
one Na þ channel blocker insecticide (SCBI) binding site per<br />
channel, but the number <strong>of</strong> batrachotoxin (BTX) <strong>and</strong> pyrethroid<br />
sites is not certain, although only one <strong>of</strong> each is shown. All<br />
three drug sites are in the middle <strong>of</strong> the S6 segments, <strong>and</strong> the<br />
pyrethroid site also includes residues in segment 5.<br />
Table 2 Action <strong>of</strong> DCJW <strong>and</strong> indoxacarb on the abdominal<br />
stretch receptor organ <strong>of</strong> Spodoptera frugiperda<br />
Average percent block<br />
(five preparations, in exposure)<br />
Concentration a (M) DCJW Indoxacarb<br />
3e-9 0 0<br />
1e-8 40 0<br />
3e-8 100 25<br />
1e-7 100 60<br />
3e-7 100 100<br />
a In a saline containing, in mM, 28 NaCl, 16 KCl, 9 CaCl2, 1.5<br />
NaH 2PO 4, 1.5 mgCl 2, <strong>and</strong> 175 sucrose, pH 6.5, the stretch<br />
receptor fired continuously for several hours between 25 <strong>and</strong><br />
75 Hz.<br />
The actions <strong>of</strong> indoxacarb <strong>and</strong> DCJW were also<br />
compared quantitatively on the abdominal stretch<br />
receptor organs <strong>of</strong> S. frugiperda (Table 2). In this<br />
preparation, the insecticides in solution are perfused<br />
rapidly over the body wall containing the<br />
stretch receptor, a small, thin organ directly exposed<br />
to the saline. Significant metabolism in this preparation<br />
is unlikely, but cannot be excluded. The organ<br />
fires continually at a rate <strong>of</strong> between 25 <strong>and</strong> 75 Hz<br />
for many hours, <strong>and</strong> is very sensitive to block by<br />
SCBIs. DCJW blocked activity consistently within<br />
20–40 min at 3 10 8 M, but in five tests at 10 8 M<br />
2: Indoxacarb <strong>and</strong> the Sodium Channel Blocker <strong>Insect</strong>icides 49<br />
the average percent block within 1 h was 40%.<br />
Indoxacarb was also intrinsically active, but 3- to<br />
10-fold weaker than DCJW, blocking consistently at<br />
3 10 7 M, but only 60% within 1 h at 1 10 7 M<br />
<strong>and</strong> 25% at 3 10 8 M.<br />
In conclusion, it appears that indoxacarb is weaker<br />
(about three to ten times) than DCJW on Na þ channels,<br />
<strong>and</strong> that the block is readily reversible. Furthermore,<br />
the much slower effect <strong>of</strong> indoxacarb on the<br />
compound action potentials in M. sexta ganglia in<br />
comparison with DCJW indicates that indoxacarb<br />
enters the ganglion much more slowly than does<br />
DCJW. Based on the appearance <strong>of</strong> insect symptoms<br />
concurrent with the appearance <strong>of</strong> high levels <strong>of</strong> metabolically<br />
formed DCJW in larval Lepidoptera (Wing<br />
et al., 1998, 2000) <strong>and</strong> the greater potency <strong>and</strong> irreversibility<br />
<strong>of</strong> DCJW Na þ channel block, it appears<br />
that the toxicologically significant compound after<br />
indoxacarb or DPX-JW062 administration is DCMP<br />
or DCJW, respectively.<br />
2.4.9. Effects <strong>of</strong> SCBIs on Alternative Target Sites<br />
Other possible target sites for SCBIs have been<br />
considered. The voltage-gated Ca 2þ channel a subunits<br />
belong to the same protein superfamily as the<br />
voltage-gated Na þ channels, <strong>and</strong> have a similar<br />
structure, composed <strong>of</strong> 24 transmembrane segments<br />
arranged into four domains <strong>of</strong> six segments each.<br />
Not unexpectedly, Ca 2þ channels were also found<br />
to be blocked by pyrazolines, although at higher<br />
concentrations than Na þ channels (Zhang <strong>and</strong><br />
Nicholson, 1993; Zhang et al., 1996). So far, there<br />
is no evidence that Ca 2þ channel effects are significant<br />
in insect poisoning. In the initial work<br />
on the pyrazolines, it was observed in paralyzed<br />
cockroaches <strong>and</strong> M. sexta larvae that the heart<br />
continued to beat normally, <strong>and</strong> conduction across<br />
the cholinergic cercal–giant fiber synapses as well<br />
as g-aminobutyric acid (GABA) <strong>and</strong> glutamate<br />
synapses on muscle, all Ca 2þ channel-dependent processes,<br />
functioned normally (Salgado, 1990). Furthermore,<br />
DCJW had no effect on low-voltage activated<br />
<strong>and</strong> high-voltage activated calcium currents in isolated<br />
cockroach neurons (Lapied et al., 2001).<br />
A strong hyperpolarization <strong>of</strong> M. sexta muscle,<br />
on the order <strong>of</strong> 20 mV, was observed after poisoning<br />
by pyrazolines (Salgado, 1990). The effect was not<br />
reversible with prolonged washing <strong>and</strong> could not<br />
be reproduced by treatment with pyrazoline in solution,<br />
<strong>and</strong> therefore appears to be secondary <strong>and</strong> not<br />
related to the hyperpolarization <strong>of</strong> DUM neurons<br />
observed by Lapied et al. (2001). Muscles <strong>of</strong> Periplaneta<br />
or Musca were not hyperpolarized during<br />
pyrazoline poisoning (Salgado, 1990).