High affinity binding of pyrethroids to the � subunit of brain sodium channels

SUMMARY Na ϩ channels are the primary molecular targets of the pyrethroid insecticides. Na ϩ channels consisting of only a type IIA ␣ subunit expressed in Chinese hamster ovary cells responded to pyrethroid treatment in a normal manner: a sustained Na ϩ current was induced progressively after each depolarizing pulse in a train of stimuli, and this Na ϩ current decayed slowly on repolarization. These modified Na ϩ channels could be reactivated at much more negative membrane potentials (V 0.5 ϭ Ϫ139 mV) than unmodified Na ϩ channels (V 0.5 ϭ Ϫ28 mV). These results indicate that pyrethroids can modify the functional properties of the Na ϩ channel ␣ subunit expressed alone by blocking their inactivation, shifting their voltage dependence of activation, and slowing their deactivation. To demonstrate directly the specific interaction of pyrethroids with the ␣ subunit of voltage-gated Na ϩ channels, a radioactive photosensitive derivative, [ 3 H]RU58487, was used in binding and photolabeling studies. In the presence of a low concentration of the nonionic detergent Triton X-100, specific pyrethroid binding to Na ϩ channels in rat brain membrane preparations could be measured and reached 75% of total binding under optimal conditions. Binding approached equilibrium within 1 hr at 4°, dissociated with a half-time of ϳ10 min, and had K D values of ϳ58 -300 nM for three representative pyrethroids. Specific pyrethroid binding was enhanced by ϳ40% in the presence of 100 nM ␣-scorpion toxin, but no allosteric enhancement was observed in the presence of toxins acting at other Na ϩ channel receptor sites. Extensive membrane washing increased specific binding to 89%. Photolabeling with [ 3 H]RU58487 under these optimal binding conditions revealed a radiolabeled band with an apparent molecular mass of 240 kDa corresponding to the Na ϩ channel ␣ subunit. Anti-peptide antibodies recognizing sequences within the ␣ subunit were able to specifically immunoprecipitate the covalently modified channel. Together, these results demonstrate that the pyrethroids can modify the properties of cells expressing only the ␣ subunit of Na ϩ channels and can bind specifically to a receptor site on the ␣ subunit

Neustonic versus epiphytic bacteria of eutrophic lake and their biodegradation ability on deltamethrin

This study evaluated biodegradation of the insecticide deltamethrin (1 μg l−1) by pure cultures of neustonic (n = 25) and epiphytic (n = 25) bacteria and by mixed cultures (n = 1), which consisted of a mixture of 25 bacterial strains isolated from the surface microlayer (SM ≈ 250 μm) and epidermis of the Common Reed (Phragmites australis, (Cav.) Trin. ex Steud.) growing in the littoral zone of eutrophic lake Chełmżyńskie. Results indicate that neustonic and epiphytic bacteria are characterized by a similar average capacity to degrade deltamethrin. After a 15-day incubation, bacteria isolated from the surface microlayer reduced the initial concentration of deltamethrin by 60%, while the average effectiveness of the bacteria found on the Common Reed equaled 47%

Review of Pesticide Urinary Biomarker Measurements from Selected US EPA Children’s Observational Exposure Studies

Children are exposed to a wide variety of pesticides originating from both outdoor and indoor sources. Several studies were conducted or funded by the EPA over the past decade to investigate children’s exposure to organophosphate and pyrethroid pesticides and the factors that impact their exposures. Urinary metabolite concentration measurements from these studies are consolidated here to identify trends, spatial and temporal patterns, and areas where further research is required. Namely, concentrations of the metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol or TCPy), diazinon (2-isopropyl-6-methyl-4-pyrimidinol or IMP), and permethrin (3-phenoxybenzoic acid or 3-PBA) are presented. Information on the kinetic parameters describing absorption and elimination in humans is also presented to aid in interpretation. Metabolite concentrations varied more dramatically across studies for 3-PBA and IMP than for TCPy, with TCPy concentrations about an order of magnitude higher than the 3-PBA concentrations. Temporal variability was high for all metabolites with urinary 3-PBA concentrations slightly more consistent over time than the TCPy concentrations. Urinary biomarker levels provided only limited evidence of applications. The observed relationships between urinary metabolite levels and estimates of pesticide intake may be affected by differences in the contribution of each exposure route to total intake, which may vary with exposure intensity and across individuals

Straightforward synthesis of isopropylidenediphenylsulfurane and application to industrially viable stereoselective synthesis of deltamethrin insecticide

peer reviewedWe describe three stereoselective syntheses of deltametrin, one of the most potent industrially available insecticides, from γ-alkoxy-α,β-unsaturated carbonyl compounds, isopropyldiphenylsulfonium tetrafluoroborate and potassium tert-butoxide

Synthesis of Alkylidene(<i>gem</i>-Difluorocyclopropanes) from Propargyl Glycolates by a One-Pot Difluorocyclopropenation/Ireland–Claisen Rearrangement Sequence

A one-pot difluorocyclopropenation/Ireland–Claisen rearrangement sequence applied to readily available propargyl glycolates was developed as a route toward functionalized alkylidene­(<i>gem</i>-difluorocyclopropanes). This strategy conveniently avoids the isolation of the unstable 3,3-difluorocyclopropenylcarbinyl glycolates arising from the difluorocyclopropenation. The Ireland–Claisen rearrangement proceeds with high diastereoselectivity and chirality transfer to afford alkylidene­(<i>gem</i>-difluorocyclopropanes) incorporating a quaternary stereocenter and a protected glycolic acid moiety, which are useful building blocks for the preparation of functionalized <i>gem</i>-di­fluoro­cyclo­propanes